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Background: Digestive system cancers pose a significant global health challenge with high incidence and mortality rates. Inflammation is a key factor in cancer progression, necessitating reliable prognostic indicators. The pan-immune-inflammation value (PIV), as a new biomarker of immune-inflammatory response, has emerged as a potential prognostic biomarker for cancers. Methods: We performed a meta-analysis to evaluate the prognostic significance of PIV in digestive system cancers. Our search, up to June 2024, included 20 studies from 19 articles with 5037 patients. We extracted and analyzed data on PIV levels and assessed hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), recurrence-free survival (RFS), and cancer-specific survival (CSS) using STATA 14.0. Results: Our analysis found that high PIV levels were significantly associated with poor prognosis in patients with digestive system cancers. Specifically, high PIV was linked to shorter OS (HR = 2.039, P < 0.001), PFS (HR = 1.877, P = 0.028), DFS (HR = 1.624, P = 0.005), RFS (HR = 2.393, P = 0.037), and CSS (HR = 2.053, P < 0.001). Additionally, the adverse prognostic impact of high PIV on OS was consistent across different cancer types, including digestive tract, colorectal, esophageal, and hepatobiliary pancreatic cancers. Although some heterogeneity was observed, sensitivity and bias analyses confirmed the reliability of these findings. Conclusions: PIV was a valuable and practical prognostic marker for digestive system cancers, providing significant predictive value across multiple survival metrics. Its simplicity and minimal invasiveness nature support its potential integration into routine clinical practice. [ABSTRACT FROM AUTHOR]

Background: Advanced-stage non-small cell lung cancer (NSCLC) poses treatment challenges, with immune checkpoint inhibitors (ICIs) as the main therapy. Emerging evidence suggests the gut microbiome significantly influences ICI efficacy. This study explores the link between the gut microbiome and ICI outcomes in NSCLC patients, using metatranscriptomic (MTR) signatures. Methods: We utilized a de novo assembly-based MTR analysis on fecal samples from 29 NSCLC patients undergoing ICI therapy, segmented according to progression-free survival (PFS) into long (> 6 months) and short (≤ 6 months) PFS groups. Through RNA sequencing, we employed the Trinity pipeline for assembly, MMSeqs2 for taxonomic classification, DESeq2 for differential expression (DE) analysis. We constructed Random Forest (RF), Support Vector Machine (SVM), and Extreme Gradient Boosting (XGBoost) machine learning (ML) algorithms and comprehensive microbial profiles. Results: We detected no significant differences concerning alpha-diversity, but we revealed a biologically relevant separation between the two patient groups in beta-diversity. Actinomycetota was significantly overrepresented in patients with short PFS (vs long PFS, 36.7% vs. 5.4%, p < 0.001), as was Euryarchaeota (1.3% vs. 0.002%, p = 0.009), while Bacillota showed higher prevalence in the long PFS group (66.2% vs. 42.3%, p = 0.007), when comparing the abundance of corresponding RNA reads. Among the 120 significant DEGs identified, cluster analysis clearly separated a large set of genes more active in patients with short PFS and a smaller set of genes more active in long PFS patients. Protein Domain Families (PFAMs) were analyzed to identify pathways enriched in patient groups. Pathways related to DNA synthesis and Translesion were more enriched in short PFS patients, while metabolism-related pathways were more enriched in long PFS patients. E. coli-derived PFAMs dominated in patients with long PFS. RF, SVM and XGBoost ML models all confirmed the predictive power of our selected RNA-based microbial signature, with ROC AUCs all greater than 0.84. Multivariate Cox regression tested with clinical confounders PD-L1 expression and chemotherapy history underscored the influence of n = 6 key RNA biomarkers on PFS. Conclusion: According to ML models specific gut microbiome MTR signatures' associate with ICI treated NSCLC outcomes. Specific gene clusters and taxa MTR gene expression might differentiate long vs short PFS. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have been the standard treatment for patients with sensitizing EGFR mutation. However, almost all patients eventually acquire resistance to EGFR-TKIs. Therefore, easily available parameters to estimate the outcome of lung adenocarcinoma patients treated with EGFR-TKIs are in urgent need. Lung adenocarcinoma patients harbored EGFR sensitive mutant and received EGFR-TKIs as first-line or second-line treatment were recruited in the study. X-tile software were utilized to determine the optimal cut-off value of Alkaline phosphatase (ALP), direct bilirubin (DB), total bile acid (TBA), and high-density lipoprotein-cholesterol (HDL-C). The prognostic value of ALP, DB, TBA, and HDL-C for Progression-free survival (PFS) in patients were evaluated by the Kaplan-Meier curve. We applied univariate and multivariate survival analysis to identify the independent predictor for PFS in patients with EGFR-mutant advanced lung adenocarcinoma and received EGFR-TKIs. A total of 131 lung adenocarcinoma patients with a median age of 58 years old were included in the final analysis. Patients with elevated level of DB and HDL-C showed a longer PFS, while high level of ALP and TBA indicated shorter PFS in response to EGFR-TKI treatment. The multivariate survival analyses revealed a significant association of prolonged PFS with increased DB, and decreased TBA. In conclusion, these findings suggest that DB and TBA were significant independent predictors of PFS in EGFR-TKI-treated patients with advanced lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted thoracoscopic surgery (RATS) thymectomy has been increasingly performed for treating thymic epithelial tumors in recent years. However, there are very limited reports on the long-term oncologic outcomes after RATS thymectomy, particularly in comparison to Video-assisted thoracoscopic surgery (VATS). This study aimed to compare the perioperative and long-term oncological outcomes between RATS and VATS. Methods: The study was conducted on 180 consecutive patients undergoing RATS or VATS between July 2016 and December 2019, 85 of whom underwent RATS, and 95 of whom underwent VATS. A 1:1 matched propensity score-matched analysis was performed and the perioperative and long-term oncologic outcomes of the two groups compared. Result: RATS group experienced a shorter operation time (median: 100 min vs. 120 min; P = 0.039) and less blood loss (40.00 ml vs. 50.00 ml, P = 0.011). RATS demonstrated a significantly lower conversion rate to open surgery compared to VATS, with only two patients requiring conversion in the RATS group as opposed to ten patients in the VATS group (3.03% vs. 15.15%, P = 0.030). In the RATS group, the 5-year progression-free survival rate was 87.70%, and the 5-year tumor-related survival rate was 92.31%, demonstrating no statistically significant difference compared to those in the VATS group. Conclusion: Compared with VATS, robotic thymectomy demonstrated excellent perioperative outcomes, and RATS achieved long-term oncologic outcomes comparable to those of VATS. RATS thymectomy could be considered as an effective alternative approach for treating thymic epithelial tumors. [ABSTRACT FROM AUTHOR]

Peritoneal metastasis (PM) is a common metastasis site and death cause of gastric cancer, which is a complex biological process, but there is currently a lack of effective prediction and treatment targets. In this study, we first analyzed the differential gene expression of gastric cancer patients with or without peritoneal metastasis, and identified the HECT domain E3 ubiquitin protein ligase 2 (HECTD2) as the core gene of PM in gastric cancer. The current study shows that the role of HECTD2 in tumor is contradictory. In this study, our results show that the low expression of HECTD2 indicates that the survival rate of overall survival (OS), progression-free survival (PFS), disease-specific survival (DSS), and disease-free survival (DFS) are better, and can be used as an important component of prognostic indicators. In addition, through pathway enrichment analysis, we found that HECTD2 was mainly involved in metastasis related pathways such as extracellular matrix remodeling and cell adhesion in gastric cancer, and high expression of HECTD2 could activate epithelial-mesenchymal transition (EMT) metastasis related pathways in gastric cancer. In regulating the metastasis of gastric cancer cells, HECTD2 can also change the surrounding microenvironment, induce the enrichment of interstitial components and build an immune microenvironment conducive to tumor progression, while patients with low expression of HECTD2 may be more likely to benefit from immunotherapy. In conclusion, HECTD2 may be a novel biomarker for the diagnosis and prognosis of peritoneal metastasis of gastric cancer, providing basis for the mechanism of peritoneal metastasis of cancer and clinical medication. [ABSTRACT FROM AUTHOR]

Objective: To assess the characteristics, molecular classification, and role of adjuvant treatment in patients with endometrioid endometrial cancer (EEC) and microcystic elongated and fragmented (MELF) myometrial invasion pattern. Methods: This study included patients who were diagnosed with EEC with a MELF invasion pattern and underwent surgery from January 2019 to December 2023. We analyzed molecular classification, clinicopathological characteristics, and prognostic outcomes, including recurrence and adjuvant therapy. Results: Out of 529 patients, 84 (15.9%) exhibited the MELF pattern, with 1 (1.2%) classified as POLE-mutation, 19 (22.6%) as mismatch repair deficient, 53 (63.1%) as no specific molecular profile, and 11 (13.1%) as p53-mutant subtype. Fifty (59.5%) patients with MELF invasion pattern received adjuvant chemotherapy (CT) ± external beam radiation therapy (EBRT), 19 (22.6%) received EBRT only, and 15 (17.9%) received no adjuvant treatment. Receiving adjuvant therapy was significantly associated with the risk level defined by the ESMO guideline for endometrial cancer (p = 0.002). With a median follow-up of 26 months (range: 1–59), the progression-free survival at 3-years for the MELF invasion patients was 91%. Seven patients with the MELF pattern experienced recurrence, of whom one was in stage IA (low risk, local recurrence) and did not receive any additional treatment, two were in stage IB (intermediate / high-intermediate risk, distant recurrence) and received EBRT only and the remaining four were in stage III to IV and had distant recurrence despite receiving adjuvant chemotherapy with or without EBRT. Among 43 intermediate- and high-intermediate-risk EEC patients, receiving CT ± EBRT was significantly associated with better DFS than without CT (p = 0.047). Conclusion: The presence of the MELF pattern in EEC should be incorporated into decision-making regarding adjuvant therapy. The use of adjuvant treatment should be tailored based on histology and molecular type. [ABSTRACT FROM AUTHOR]

Background: The primary tumor resection (PTR) of de novo stage IV breast cancer (DnIV BC) is controversial, and previous studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) could be a poor-prognosis factor for BC. We investigated PTR's surgical advantage related to clinical outcomes, the surgery timing in responders to systemic therapy, and whether the NLR can predict the benefit of surgery for DnIV BC. Patients and methods: We retrospectively analyzed the cases of the DnIV BC patients who received systemic therapies and/or underwent PTR at our institution between January 2004 and December 2022. Blood tests and NLR measurement were performed before and after each systematic therapy and/or surgery. Results: Sixty patients had undergone PTR local surgery (Surgery group); 81 patients had not undergone surgical treatment (Non-surgery group). In both groups, systemic treatment was performed as chemotherapy (95%) and/or endocrine therapy (92.5%) (p < 0.0001). The groups' respective median progression-free survival (PFS) durations were 88 and 30.3 months (p = 0.004); their overall survival (OS) durations were 100.1 and 31.8 months (p = 0.0002). The Surgery-group responders to systemic therapy lasting > 8.1-months showed significantly longer OS (p = 0.044). The PFS and OS were significantly associated with the use of postoperative systemic therapy (p = 0.0012) and the NLR (p = 0.018). A low NLR (≤ 3) was associated with significantly better prognoses (PFS and OS; p < 0.0001). Conclusions: A longer effective duration of systemic therapy (> 8.1 months) and a low pre-surgery NLR (≤ 3.0) could predict PTR's surgical advantage for DnIV BC. These variables may help guide decisions regarding the timing of surgery for DnIV BC. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholangiocarcinoma (ICC) is a challenging primary liver cancer with a poor prognosis, especially in unresectable cases. Traditional palliative irradiation is limited in reducing liver doses. This study aimed to evaluate the efficacy and toxicity of respiratory-gated proton beam therapy without fiducial markers for intrahepatic cholangiocarcinoma. Methods: Between October 2011 and February 2022, 24 patients (median [range] age, 71 [41–88] years) were evaluated at our institution. Twelve patients were pathologically diagnosed with ICC. All patients underwent respiratory-gated proton beam therapy at a dose of 48–83.6 (relative biological effectiveness) in 20–38 fractions with four-dimensional computed tomography planning. The median follow-up period was 18.5 (range, 2.0–74.0) months. The median tumor size was 41 (range, 10–134) mm. Twenty-one patients were classified as having Child–Pugh class A, and three patients were classified as having Child–Pugh class B. Local progression was defined as any growth of the irradiated tumor. Results: The median survival time was 28 months for all patients. The Kaplan–Meier estimates of the 2-year overall survival, progression-free survival, and local tumor control rates were 51%, 26%, and 73%, respectively. Local tumor control rates were non-inferior to those reported in previous studies using fiducial markers. One patient had grade 4 pleural effusion; however, whether this was an adverse event due to the proton beam therapy was unclear. Conclusions: Respiratory-gated proton beam therapy without fiducial markers is an effective and less invasive treatment option for ICC, showing potential for improved local control and tolerable adverse effects. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy and immunotherapy for non-small-cell lung cancer (NSCLC) are gaining momentum. However, its long-term efficacy remains limited to only a small fraction of patients. Hence, it is crucial to identify reliable immunohistochemical biomarkers to facilitate the formulation of optimal treatment strategies and to predict therapeutic outcomes. Methods: We retrospectively analyzed a cohort of 140 patients diagnosed with NSCLC who received chemotherapy or immunotherapy. Using bioinformatics analysis and machine learning techniques, we assessed the role of immunohistochemical biomarkers and clinical characteristics in developing a predictive model for treatment options and outcomes in this population. Results: Our research has found that immunohistochemical biomarkers can accurately predict treatment regimens and progression-free survival in NSCLC patients with an accuracy rate of 82.1%. We identified an exclusive detection panel for the six vital biomarkers. Of particular note is the role of programmed cell death protein 1 ligand 1 (PD-L1) expression in guiding treatment selection, with high expression predicting better outcomes in the immunotherapy group at a cut-off value of 50%. Non-squamous patients who tested positive for thyroid transcription factor 1 had a longer median progression-free survival, while squamous patients who tested positive for p63 protein or cytokeratin 5/6 expression had a longer median progression-free survival. Conclusions: The results of our study are highly encouraging, as they revealed a significant correlation between immunohistochemical biomarkers, therapeutic regimens, and prognosis. These findings indicate that our immunohistochemical detection panel has great potential for facilitating customization of therapeutic regimens to improve patient care. The insights gained from this study could help clinicians optimize treatment protocols and ultimately enhance clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Several studies have confirmed the potential value of applying radiomics to predict prognosis of breast cancer. However, the tumor segmentation in these studies depended on delineation or annotation of breast cancer by radiologist, which is often laborious, tedious, and vulnerable to inter- and intra-observer variability. Automatic segmentation is expected to overcome this difficulty. Herein, we aim to investigate the value of automatic segmentation-based multi-modal radiomics signature and magnetic resonance imaging (MRI) features in predicting disease-free survival (DFS) of patients diagnosed with invasive breast cancer. Methods: This retrospective multicenter study included a total of 643 female patients with invasive breast cancer who underwent preoperative ultrasound (US) and MRI for prognostic analysis. Data (n = 480) from center 1 were divided into training and internal testing sets, while data (n = 163) from centers 2 and 3 were analyzed as the external testing set. We developed automatic segmentation frameworks for tumor segmentation by deep learning. Then, Least absolute shrinkage and selection operator Cox regression was used to select features to construct radiomics signature, and corresponding radiomics score (Rad-score) was calculated. Finally, six models for predicting DFS were constructed by using Cox regression and assessed in terms of discrimination, calibration, and clinical usefulness. Results: The multi-modal radiomics signature combining intra- and peri-tumoral radiomics signatures of US and MRI achieved a higher C-index in the internal (0.734) and external (0.708) testing sets than most other radiomics signatures in predicting DFS, and successfully stratified patients into low- and high-risk groups. The multi-modal clinical imaging model combining the multi-modal Rad-score and clinical traditional MRI model-score resulted in a higher C-index (0.795) than other models in the external testing set, and it had a better calibration and higher clinical benefit. Conclusions: This study demonstrates that the multi-modal radiomics signature derived from automatic segmentations of US and MRI is a promising risk stratification biomarker for breast cancer, and highlights that the appropriate combination of multi-modal radiomics signature, clinical characteristics, and MRI feature can improve performance of individualized DFS prediction, which might assist in guiding decision-making related to breast cancer. [ABSTRACT FROM AUTHOR]

Aims: We analysed the survival, complications, and function of frozen autograft augmented with intramedullary cement and bridging plates fixation for intercalary bone defect reconstruction in primary bone sarcomas. Patients and Methods: A retrospective cohort study was conducted on 72 patients with primary bone sarcomas (34 males, 38 females) between January 2016 and June 2023. The average age was 22.0 ± 13.6 years (6 to 61 years) and the pathological type included osteosarcoma (55), followed by adamantinoma (5), Ewing's sarcoma (4), undifferentiated pleomorphic sarcoma (4), chondrosarcoma (3), and malignant tenosynovial giant cell tumor (1). The oncological outcomes included local control, metastasis, progression-free survival and overall survival. The functional outcomes were evaluated by the Musculoskeletal Tumor Society Score (MSTS-93), the Toronto Extremity Salvage Score (TESS), and the motion of the joint. Results: The mean follow-up time was 50.0 ± 27.4 months (12 to 99 months). 10 patients died of the disease, 9 patients were alive with disease and 53 patients were alive with no evidence of disease. The average 5-year overall survival of autograft was 85.8% (95% CI, 72.1-93.1%). The average MSTS-93 score was 96% (67–100%) and the average TESS score was 98% (74–100%). Twenty-four patients (33.3%) had at least one complication in the follow-up period. The most common complications were nonunion (9.7%, 7/72) and local recurrence (9.7%, 7/72), followed by leg length discrepancy (6.9%, 5/72), infection (5.6%, 4/72), implant failure (4.2%, 3/72), delayed union (2.8%, 2/72), and graft fractures (1.4%, 1/72). Tumor site was an independent risk factor for bone nonunion (OR, 22.23; p = 0.006). Conclusions: We presented a large technique series for preventing autograft-related complications (especially for autograft fractures) of intercalary frozen autograft reconstruction. This method showed promising functional outcomes and provided durable reconstruction. Level of evidence: level IV therapeutic study. [ABSTRACT FROM AUTHOR]

Background: The major breakthrough in cancer therapy with immune checkpoint inhibitors (ICIs) has highlighted the important role of immune checkpoints in antitumoral immunity. However, most patients do not achieve durable responses, making biomarker research in this setting essential. CD27 is a well known costimulatory molecule, however the impact of its soluble form in ICI is poorly investigated. Therefore, we aimed at testing circulating concentrations of soluble CD27 (sCD27) and CD27 bound to extracellular vesicles (EVs) as potential biomarkers to predict response and overall survival (OS) in patients undergoing ICI. Methods: Serum and plasma levels of sCD27 were assessed by immunoassay in three patient cohorts (n = 187) with advanced solid malignancies including longitudinal samples (n = 126): a training (n = 84, 210 specimens, Aachen ICI) and validation cohort (n = 70, 70 specimens, Hamburg ICI), both treated with ICI therapy, and a second independent validation cohort (n = 33, 33 specimens, Hamburg non-ICI) undergoing systemic therapy without any ICI. In a subset (n = 36, 36 baseline and 108 longitudinal specimens), EV-bound CD27 from serum was measured, while EV characterization studies were conducted on a fourth cohort (n = 45). Results: In the Aachen and Hamburg ICI cohorts, patients with lower circulating sCD27 levels before and during ICI therapy had a significantly longer progression-free survival (PFS) and OS compared to patients with higher levels, a finding that was confirmed by multivariate analysis (MVA) (Aachen ICI: pPFS = 0.012, pOS = 0.001; Hamburg ICI: pPFS = 0.040, pOS = 0.004) and after randomly splitting both cohorts into training and validation. This phenomenon was not observed in the Hamburg non-ICI cohort, providing a rationale for the predictive biomarker role of sCD27 in immune checkpoint blockade. Remarkably, EV-bound CD27 baseline levels and dynamics during ICI therapy also emerged as potent predictive biomarkers, acting however antagonistically to soluble sCD27, i.e. higher levels were associated with PFS and OS benefit. Combining both molecules ("multi-CD27" score) enhanced the predictive ability (HRPFS: 17.21 with p < 0.001, HROS: 6.47 with p = 0.011). Conclusion: Soluble and EV-bound CD27 appear to have opposing immunomodulatory functions and may represent easily measurable, non-invasive prognostic markers to predict response and survival in patients undergoing ICI therapy. [ABSTRACT FROM AUTHOR]

Background: Postoperative radiotherapy (PORT) is crucial for patients with thoracic locally advanced esophageal squamous cell carcinoma (LA-ESCC, pT3-4aN0-3M0) following esophagectomy. However, the appropriate radiation volume has not been well established. This study aimed to determine the optimal PORT volume for LA-ESCC patients. Methods: LA-ESCC patients post-esophagectomy were randomly assigned to either the large-field irradiation (LFI, primary lesion and lymph node tumor bed plus elective nodal irradiation) group or the small-field irradiation (SFI, primary lesion and lymph node tumor bed alone) group. Stratification was based on T stage and the number of lymph node metastases. The primary endpoint was disease-free survival (DFS), while the secondary endpoints included overall survival (OS), adverse events, and patterns of initial failure. Results: A total of 401 patients were randomly assigned to the intention-to-treat analysis(LFI group, n = 210; SFI group, n = 191). The median DFS of patients in the LFI group was 47.9 months and 48.1 months in the SFI group (HR = 0.87, 95%CI, 0.65 to 1.16; p = 0.32). The estimated one-year and three-year OS rates were 89.2% and 63.2% for patients in the LFI group, compared to 86.6% and 60.7% for the SFI group, respectively. The difference of OS between the two groups was not significant (HR = 0.86, 95%CI, 0.63 to 1.16; p = 0.35). Fewer patients in the LFI group experienced locoregional recurrence compared to the SFI group (12.9% vs 20.4%, p = 0.013). Additionally, locoregional recurrence-free survival of the LFI group was significantly longer than that of SFI group (HR = 0.54, 95%CI, 0.34–0.87; p = 0.01). The most common toxicity was grade 2 esophagitis, observed in 22.9% of the LFI group and 16.8% of the SFI group. Grade 3 adverse events occurred in 6.7% of the LFI group and 2.6% of the SFI group. No grade 4 or 5 toxicities were observed. Adverse events did not significantly differ between the two groups. Conclusions: Postoperative radiotherapy, with the specified radiation volume shows encouraging survival outcomes that are comparable to those of neoadjuvant chemoradiotherapy in patients with thoracic LA-ESCC. Both postoperative irradiation fields were found to be feasible and safe. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for non-small cell lung cancer (NSCLC). The variability in patient responses necessitates a blood-based, multi-cohort gene signature to predict ICI response in NSCLC. Methods: We performed transcriptomic profiling of peripheral blood mononuclear cell (PBMC) and buffy coat (BC) samples from three independent cohorts of NSCLC patients treated with ICIs: a retrospective cohort (PMBCR, n = 59), a retrospective validation cohort (BC, n = 44), and a prospective validation cohort (PBMCP, n = 42). We identified a 5-gene signature (UQCRB, NDUFA3, CDKN2D, FMNL1-DT, and APOL3) predictive of ICI response and validated its clinical utility in the prospective PBMCP cohort. Response was evaluated using RECIST criteria, and patients were followed up for progression-free survival (PFS) and overall survival (OS). Results: In the prospective PBMCP cohort, the 5-gene signature demonstrated high accuracy in stratifying patients into responders and non-responders (AUC = 0.89, 95% CI: 0.80–0.99). Predicted responders exhibited significantly longer PFS compared to predicted non-responders (median: 13.8 months vs. 4.2 months, HR = 0.21, 95% CI: 0.07–0.58, p = 0.005). Conclusion: Our study confirms a 5-gene signature as a key biomarker for ICI response in NSCLC, enhancing treatment precision. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prognostic value of visible hematuria in T1a renal cell carcinoma (RCC). Materials and methods: In the RCC database of the Chinese People's Liberation Army General Hospital Department of Urology, we assembled the records of patients with unilateral RCC over 18 years of age diagnosed between 2008 and 2019. The clinical stage was cT1, and the tumors ranged in size from 0 to 7 cm. The primary treatments were partial nephrectomy (PN) or radical nephrectomy (RN). Logistic regression analysis, Cox regression, interaction analysis, and Kaplan-Meier survival analysis were used to study the correlation between visible hematuria and progression-free survival (PFS), and cancer-specific survival (CSS). Results: A total of 7,610 patients with cT1 RCC comprised the study population, including 505 RCC patients with visible hematuria. The average follow-up time was 64.6 months (range: 12–144 months). Visible hematuria was significantly associated with the prognosis (PFS, hazard ratio [HR] = 2.7, P < 0.001; CSS, HR = 4.2, P < 0.001) of T1a RCC, but was more significant for CSS in cases of a tumor size ≤ 2 cm (HR = 26.8, P = 0.026). This effect was not significant in T1b RCC (PFS, HR = 0.7, P = 0.153; CSS, HR = 1.1, P = 0.862). The interaction between visible hematuria and tumor size was significant (P = 0.001). Conclusions: This study showed that visible hematuria was an independent risk factor for PFS and CSS in T1a RCC. The predictive value of visible hematuria for CSS was more significant in RCCs ≤ 2 cm, but did not reach statistical significance in T1b RCC. T1a RCC patients with visible hematuria should be intensively monitored during follow-up. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to systematically analyze the efficacy and toxicity of lurbinectedin as a second-line or subsequent treatment for extensive-stage small cell lung cancer (ES-SCLC). Methods: Candidate studies were identified in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang databases up to 1 May 2024. Objective remission rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted, respectively. The efficacy and toxicity of lurbinectedin in ES-SCLC were analyzed by meta-analysis. Results: Six eligible prospective studies were included in this meta-analysis, including 536 patients with ES-SCLC who received second-line or subsequent treatment. In pooled analysis, the ORR of lurbinectedin was 35% (95% confidence interval [CI] 29–41), DCR was 67% (95%CI 58–76), DOR was 5.33 months (95%CI 4.51-6.16), PFS was 3.38 months (95%CI 2.59-4.17), and OS was 7.49 months (95%CI 5.11–9.87). The incidence of AEs and severe adverse events (SAEs) was 92% (95%CI 78–100) and 37% (95%CI 19–57), respectively. The most common AEs were leukopenia, neutropenia, anemia, and thrombocytopenia, with incidences of 81% (68–91), 74% (57–88), 73% (35–98) and 57% (46–68), respectively. Conclusion: As a promising alternative for second-line treatment for ES-SCLC, lurbinectedin has a certain level of efficacy and a favorable safety profile. The integration of lurbinectedin with other therapeutic modalities presents an emerging area warranting further investigation. [ABSTRACT FROM AUTHOR]

Background: The current treatment strategies for borderline resectable esophageal squamous cell carcinoma remain controversial. This study aimed to evaluate the efficacy and safety of programmed cell death 1 inhibitors combined with chemotherapy, followed by conversion surgery, for borderline resectable esophageal squamous cell carcinoma. Methods: Patients with borderline resectable esophageal squamous cell carcinoma treated with induction immunochemotherapy from January 1, 2020 to July 1, 2023 at our hospital were retrospectively analyzed. The primary study outcome was the R0 resection rate. Secondary study outcomes included progression-free survival (PFS), overall survival (OS), pathological complete remission (pCR) rate, and safety. Results: Forty patients with borderline resectable esophageal squamous cell carcinoma were included in the analysis. The R0 resection rate was 23/40 (57.5%); the conversion success rate was 27/40 (67.5%), and the pCR rate was 11/40 (27.5%). The median follow-up was 23.6 months (95% CI, 19.1–28.2). One-year OS and PFS rates were 77.7% and 71.8%, respectively. The incidence rate of Grade 3–4 adverse events was 10%. There was a significant difference in PFS between patients who underwent surgery and those who did not (P = 0.008, HR: 0.144 95%CI: 0.034–0.606). However, the difference in OS was not significant (P = 0.128, HR: 0.299 95%CI: 0.063–1.416). Patients who achieved clinical downstaging after induction therapy had significantly better OS (P = 0.004 h: 0.110 95%CI: 0.025–0.495) and PFS (P = 0.0016, HR: 0.106 95%CI: 0.026–0.426) compared to those who did not. Conclusions: Conversion surgery after induction immunochemotherapy is a promising new strategy with a high conversion rate, inspiring R0 resection rate, significant pathological remission rate, and mild toxicity for borderline resectable esophageal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: The Dutch Committee for the Evaluation of Oncological Drugs evaluates the effectiveness of new oncological treatments. The committee compares survival endpoints to the so-called PASKWIL-2023 criteria for palliative treatments, which define if treatment effects are considered clinically relevant. A positive recommendation depends on whether the median overall survival (OS) is below or above 12 months in the comparator arm. If the former applies, an OS benefit of at least 12 weeks, and a hazard ratio (HR) smaller than 0.7 are required. If the latter applies, an OS or progression free survival (PFS) benefit of at least 16 weeks, and an HR smaller than 0.7 are required. Nonetheless, the median survival time may not be reached and the proportional hazards (PH) assumption, quantified by the HR, is likely violated for immuno-oncology (IO) therapies, deeming these criteria inappropriate. Methods: We conducted a systematic literature review to identify statistical methods used to represent the clinical effectiveness of IO therapies based on trial data. We searched MEDLINE and EMBASE databases from inception to August 31, 2022, limited to English papers. Methodological studies, randomized controlled trials, and discussion papers recognising key issues of survival data analysis of IO therapies were eligible for inclusion. Results: A total of 1,035 unique references were identified. After full paper screening, 17 publications were included in the review. Additionally, 43 papers were identified through 'snowballing'. We conclude that the current PASKWIL-2023 criteria are methodologically incorrect under non-PH. In that case, single summary statistics fail to capture the treatment effect and any measure should be interpreted in combination with the Kaplan-Meier curves. We recommend 'parameter-free' measures, such as the difference in restricted mean survival time, avoiding assumptions on the underlying survival. Conclusions: The HR is commonly used to assess treatment effectiveness, without investigating the validity of the PH assumption. This happens with the application of the PASKWIL-2023 criteria for palliative oncology treatments, which can only be valid under a PH setting. Under non-PH, alternative treatment effect measures are suggested. We propose a step-by-step approach supporting the choice of the most appropriate methods to quantify treatment effectiveness that can be used to redefine the PASKWIL-2023 criteria, or similar criteria in other clinical areas. [ABSTRACT FROM AUTHOR]

Background and purpose: Magnetic resonance imaging is indispensable for the preoperative diagnosis of glioma. This study aimed to investigate the role of the apparent diffusion coefficient values as predictors of survival in patients with gliomas. Methods and materials: A retrospective analysis was conducted on 101 patients with gliomas who underwent surgery between 2015 and 2020. Diffusion-weighted MRI was performed before the surgery. The regions of interest were categorized into parenchymal area, non-enhancing peritumoral area, and necrotic or cystic area. All the patients were divided into three subgroups: the parenchyma group, the non-enhancing peritumoral signal abnormality group, and the necrosis or cyst group. Univariate and multivariate analyses were performed using COX regression. Results: In the parenchymal group, Ki67, P53, IDH, and the high or low ADC values were identified as independent prognosticators for disease-free survival, while Ki67, IDH, and the high or low ADC values for overall survival. In the non-enhancing peritumoral signal abnormality group, Ki67, P53, IDH, and the ADC parenchymal area/ADC non−enhancing peritumoral area ratio were identified as independent prognostic factors for disease-free survival, while Ki67, IDH, and the ADC parenchymal area/ADC non−enhancing peritumoral area ratio for overall survival. In the necrosis or cyst group, Ki67 was significantly associated with disease-free survival, while Ki67 and the ADC value of the necrotic or cystic area for overall survival. Conclusions: The ADC values, including the ADC value in the parenchymal area, the ADC parenchymal area/ADC non−enhancing peritumoral area ratio, and the ADC value in the necrotic or cystic area, can serve as an efficient and potential index for predicting the survival of patients with glioma. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy may be considered for patients with ovarian cancer (OC) whose tumors are deemed unlikely to be completely cytoreduced to no gross residual disease (R0) or who are poor surgical candidates. This Ib/II study was designed to assess the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin as neoadjuvant chemotherapy for stages III–IV, unresectable OC. Methods: Eligible patients with stage III–IV, unresectable OC were enrolled in this phase Ib/II study. All patients received neoadjuvant nab-paclitaxel (260 mg/m2, day 1, every 3 weeks) plus carboplatin (AUC 5, day 1, every 3 weeks) for 3 cycles before surgery, followed by 3–6 cycles of adjuvant chemotherapy. The phase Ib primary endpoint was safety; the phase II primary endpoint was the R0 resection rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety (for all populations). Results: Sixty-two patients were enrolled and were given neoadjuvant therapy treated between October 2019 and December 2020, of whom 9 were in the phase Ib portion and 53 in the phase II portion. A total of 53 patients underwent surgery with an R0 resection rate of 73.6% (95% CI, 59.7–84.7%). With a median follow-up of 17.5 (range 0.7–36.7) months, for all patients, the best ORR was 83.9% (95% CI, 71.7–92.4%) with 47 partial responses, the median PFS was 18.6 (95% CI, 13.8–23.3%) months, and median OS was not reached. During the neoadjuvant chemotherapy, treatment-related adverse events (TRAEs) of any grade occurred in 91.9% (57/62) of all patients. The most common hematologic TRAEs were neutropenia (55/62, 88.7%), and non-hematologic toxicity was alopecia (36/62, 58.1%). Forty-nine patients (79.0%) experienced at least one grade 3–4 TRAEs, with the most common was neutropenia (44/62, 71.0%). Besides, delays in neoadjuvant chemotherapy and surgery due to AEs were observed in 9 (1 in phase Ib; 8 in phase II) and 7 (phase II) patients, respectively. Conclusions: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant chemotherapy nab-paclitaxel plus carboplatin in stage III-IV, unresectable OC. In addition, AEs resulting in chemotherapy and surgery delays should be cautiously considered in this clinical setting. Trial registration: ClinicalTrials.gov, ChiCTR1900026893. Registered at 25 October 2019. [ABSTRACT FROM AUTHOR]

Introduction: Ovarian granulosa cell tumor (OGCT) is a rare female pathology with few available demographic data. Besides, there are no comprehensive clinical characteristics regarding the OGCT in Iran. Thus, this study aimed to assess the clinical features and survival rate of OGCT patients in Iran to expand the scope of knowledge in this field. Materials and methods: In this 10-year retrospective study (2013–2023), the cases were gathered from the oncologic clinic of women (Imam Khomeini Hospital, Tehran, Iran). The patients with definite OGCT diagnosis were selected based on the inclusion and exclusion criteria including medical history, interfering backgrounds, demographic data, histopathological assessment, clinical and para-clinical features, survival rates, and all previous medical reports for definite diagnosis of OGCT along with approved pathology samples. Results: The median age and BMI values of Iranian patients were 45 (19 ~ 83) years and 28.04 (19.4 ~ 48.0), respectively. The most common symptom was abdominal pain (56%) and 69.2% of cases were menopause. In 81.3% of cases, ovarian tumors were detected and metastasis was rare. Most patients (40.6%) underwent total abdominal hysterectomy and OGCT relapsing cases were seen in 13.2% of patients. The median of overall survival (OS) value using the Kaplan-Meier estimate was 52 months (95%CI:37.47–66.53), and the median of disease-free survival (DFS) was 45 months (95%CI: 28.88–61.12). There was a significant (p < 0.05) relation between chemotherapy and left oophorectomy with OS. A significant (p < 0.05) correlation was also detected among the OGCT stage and left oophorectomy with DFS. Conclusion: OS and DFS values showed that the OGCT in Iranian patients can be treated in most cases using two main procedures of chemotherapy and oophorectomy. Parallel application of both procedures and associated outcomes are suggested for future studies. [ABSTRACT FROM AUTHOR]

Background: Surgery is the optimal choice for early invasive mucinous lung adenocarcinoma (IMA). A systematic review and meta-analysis were conducted to explore the prognostic factors for resected IMA. Methods: We systematically reviewed the prognostic role of clinicopathological and genomic factors in resected IMA patients. Eligible studies on the treatment of IMA following the systematic search of PubMed, Embase and the Cochrane Library from January 2015 to January 2024 were identified. Outcomes of interest were overall survival (OS) and disease-free survival/recurrence-free survival (DFS/RFS). The hazard ratio (HR) and 95% confidence interval (CI) were used as impact indicators for systematic review and meta-analysis. Results: Sixteen studies involving 3,484 patients with IMA were included. The results of the combined analysis showed that male and smoking were associated with a worse prognosis. Furthermore, advanced clinical stage, poor differentiation grade, presence of visceral pleural invasion (VPI) and spread through air spaces (STAS), and presence of KRAS mutations were also associated with worse prognosis. Conclusions: Gender, smoking, clinical stage, tumor size, differentiation grading, VPI, STAS and KRAS mutation affect DFS/RFS and OS of IMA patients after surgery. Identifying these factors may aid physicians in developing more individualized treatment plans for resectable IMA patients. [ABSTRACT FROM AUTHOR]

Objective: Hepatitis B virus (HBV) infection is associated with the incidence and prognosis of diffuse large B-cell lymphoma (DLBCL), and previous studies differ in terms of clinical characteristics and prognostic factors. In this study, we explored the clinical features and prognostic characteristics of real-world DLBCL patients infected with HBV. Methods: Patients with pathologically diagnosed primary DLBCL at West China Hospital of Sichuan University were enrolled. Patients with follicular lymphoma-transformed DLBCL, primary central nervous system DLBCL, and hepatitis C virus, hepatitis E virus, human immunodeficiency virus, or syphilis infections were excluded. Ultimately, a total of 941 patients were included in this study. All patients included in the study underwent HBV serum marker testing before treatment. The demographic features, clinical characteristics and treatments of patients with different HBV infection states were collected and analyzed comprehensively to identify prognostic factors for OS and PFS. Results: Statistical analysis of the data revealed that hepatitis B surface antigen positive (HBsAg +) DLBCL patients were younger and more likely to present with advanced disease, germinal center B cell-like subtype, B symptoms and splenic involvement. There were no significant differences in OS or PFS among patients with different HBV infection statuses (χ 2 = 0.139, P = 0.933; χ2 = 0.787, P = 0.675); R-CHOP/R-CHOP-like regimens improved prognosis in HBsAg + DLBCL patients (OS: χ2 = 7.679, P = 0.006; PFS: χ2 = 9.042, P = 0.003); antiviral prophylaxis for HBsAg + DLBCL patients improved OS and PFS (HR: 0.336, P = 0.012, 95% CI [0.143, 0.788]; HR: 0.397, P = 0.032, 95% CI [0.171, 0.925]), with tenofovir treatment being particularly effective (χ2 = 4.644, P = 0.031; χ2 = 4.554, P = 0.033). Conclusions: HBsAg + DLBCL patients have unique clinical characteristics, and the use of CD20 monoclonal antibody based regimens significantly improves the outcome and prognosis of patients with HBsAg + DLBCL. Anti-HBV therapy, especially tenofovir, improves the prognosis of DLBCL patients with HBV presenting infection. Timely and sustained antiviral prophylaxis should be the standard strategy for treating DLBCL patients with HBV infection to optimize the efficacy of chemotherapy and immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Anti-angiogenic, VEGF inhibitors (VEGFi) increase progression-free survival (PFS) and, in some cases, overall survival in many solid tumours. However, their use has been compromised by a lack of informative biomarkers. We have shown that plasma Tie2 is the first tumour vascular response biomarker for VEGFi in ovarian, colorectal and gall bladder cancer: If plasma Tie2 concentrations do not change after 9 weeks of treatment with a VEGFi, the patient does not benefit, whereas a confirmed reduction of at least 10% plasma Tie2 defines a vascular response with a hazard ratio (HR) for PFS of 0.56. The aim of the VALTIVE1 study is to validate the utility of plasma Tie2 as a vascular response biomarker and to optimise the Tie2-definition of vascular response so that the subsequent randomised discontinuation VALTIVE2 study can be powered optimally. Methods: VALTIVE1 is a multi-centre, single arm, non-interventional biomarker study, with a sample size of 205 participants (176 bevacizumab-treated participants + 29 participants receiving bevacizumab and olaparib/PARPi), who are 16 years or older, have FIGO stage IIIc/IV ovarian cancer on treatment with first-line platinum-based chemotherapy and bevacizumab. Their blood plasma samples will be collected before, during, and after treatment and the concentration of Tie2 will be determined. The primary objective is to define the PFS difference between Tie2-defined vascular responders and Tie2-defined vascular non-responders in patients receiving bevacizumab for high-risk Ovarian Cancer. Secondary objectives include defining the relationship between Tie2-defined vascular progression and disease progression assessed according to RECIST 1.1 criteria and assessing the impact of PARPi on the plasma concentration of Tie2 and, therefore, the decision-making utility of Tie2 as a vascular response biomarker for bevacizumab during combined bevacizumab-PARPi maintenance. Discussion: There is an urgent need to establish a test that tells patients and their doctors when VEGFi are working and when they stop working. The data generated from this study will be used to design a second trial aiming to prove conclusively the value of the Tie2 test. Trial registration: ClinicalTrials.gov identifier: NCT04523116. Registered on 21 Aug 2020. [ABSTRACT FROM AUTHOR]

Background: The HER-2 status of breast cancer (BC) has been classified as negative or positive for a long time. Given the efficacy of novel anti-HER2-targeted antibody drug conjugates (ADCs) in HER2-low BC, a distinct subgroup of HER2-low tumors has emerged within BC. The biology and prognostic impact of HER2-low expression are not yet well defined, and inconsistent results were reported. This study aims to evaluate the impact of low HER-2 status on the response to neoadjuvant chemotherapy (NACT) and disease- free survival (DFS) rates. Methods: We retrospectively analyzed BC patients treated with NACT from 2017 to 2023 in two cancer centers. HER2-negative patients were included. HER-2 low status was defined by IHC + 1 or + 2/ISH non-amplified, and HER2-zero was defined by IHC 0. Pathological complete response (pCR) rates and DFS between HER2-low and HER2-zero populations were compared. Results: 170 patients were identified. 122 (72%) of these patients were HER2- zero BC, whereas 48 (28%) were HER2-low BC. Overall, pCR was achieved in 35 (20.5%) patients. Of these, pCR was observed in 30 patients (44.6%) from the HER2- zero group, compared to 5 patients (10.4%) from the HER2-low group (p = 0.046), but significance was lost in multivariate analysis. Among the hormone receptor (HR) positive subtype, pCR was achieved 19.8% of HER2-zero tumors and 7.5% of HER2-low tumors (p = 0.08). For HR-negative subtype 34.1% HER2-zero tumors had pCR and 25% of the HER2-low tumors had pCR (p = 0.614). There was no association between DFS and HER2-low status. Conclusions: Our study indicates that HER2-low status had no impact on pCR or DFS. [ABSTRACT FROM AUTHOR]

Background: Docetaxel (DOC) and ramucirumab (RAM) is one of the most effective regimens for advanced non-small cell lung cancer (NSCLC) treatment. In our previous study, baseline anemia was identified as a preventive factor against the development of severe adverse effects during the first treatment cycle. It was hypothesized that anemia directly promotes tumor angiogenesis, leading to the elevation of RAM efficacy with increased DOC delivery to tumors, while reducing DOC delivery to other organs, potentially mitigating severe adverse effects. If this hypothesis is correct, patients with baseline anemia may have better clinical outcomes than those with normal hemoglobin levels. In this study, we aimed to investigate the effect of baseline anemia on the efficacy of DOC + RAM in treating advanced NSCLC in a real-word setting. Methods: Patients with advanced NSCLC receiving DOC + RAM (n = 72) were retrospectively assessed. They were categorized into a control group with normal baseline hemoglobin levels and an anemia group with baseline anemia. The primary endpoint was progression-free survival (PFS) evaluation. Results: Patients in the anemia group had a significantly shorter PFS than that of patients in the control group (median PFS: 3.2 and 6.2 months; 95% confidence interval [CI]: 2.2–4.8 and 4.3–9.9 months, respectively;P = 0.008). In addition, the disease control rate in the anemia group was 65.8%, which was significantly lower than that in the control group (93.6%; P = 0.007). Overall survival tended to be shorter in patients with anemia than in controls, although the difference was not statistically significant (P = 0.07). Multivariate Cox hazard analysis suggested that baseline anemia was a singular risk factor for poor PFS (adjusted hazard ratio 1.84, 95% CI 1.08–3.13; P = 0.02). The incidence of severe adverse effects did not differ between the two groups. Conclusions: This study suggests that the PFS of patients with anemia treated with DOC + RAM for advanced NSCLC is shorter than that of those without the symptoms. [ABSTRACT FROM AUTHOR]

Background: This study aims to assess the clinical efficacy of elective neck irradiation (ENI) in patients with esthesineuroblastoma (ENB), a rare malignant neoplasm, who are clinically node-negative. Methods: We conducted a retrospective analysis of 178 patients newly diagnosed with ENB at our institution between 2009 and 2021. Propensity score matching (PSM) was employed to compare node-negative patients treated with and without ENI. We extensively examined survival outcomes and treatment failure. Results: Of the 178 participants, 149 (83.7%) were lymph node-negative and staged in Modified Kadish A-C. 96 patients underwent ENI treatment, while 53 did not. At baseline, patients who received ENI differed from those who did not in terms of radiotherapy technique, staging, orbital invasion, surgical mode, and chemotherapy. After PSM, 43 pairs were available for analysis. ENI was observed to extend overall survival (OS, 5-year 73.9% vs. 84.0%; 3-year 76.9% vs. 97.1%, p = 0.022), progression-free survival (PFS, 5-year 38.5% vs. 84.6%; 3-year 50.5% vs. 94.5%, p < 0.001) and locoregional relapse-free survival (LRFS, 5-year 42.7% vs. 84.6%, p = 0.023; 3-year 57.3% vs. 94.5%, p < 0.001) in node-negative ENI patients. Failure pattern analyses revealed that ENI, which included level Ib, II, VIIa, significantly reduced the treatment failure rate. Furthermore, ENI did not significantly impact the prognosis of T1-2 patients, indicating potential clinical value of ENI in T3-4 patients. Conclusions: Our findings suggested that ENI decreased regional failure and significantly enhanced LRFS and PFS. ENI may be considered as an integral part of the initial treatment strategy for locally advanced node-negative ENB patients. [ABSTRACT FROM AUTHOR]

Objective: Poly (ADP-ribose) polymerase (PARP) inhibitors such as olaparib and niraparib have shown promise in extending progression-free survival (PFS) in patients with platinum-sensitive recurrent (PSR) epithelial ovarian cancer. In this retrospective study, we aimed to present our own data on the effect of PARP inhibitors on PFS in recurrent epithelial ovarian cancer. Methods: 82 patients diagnosed with PSR epithelial ovarian, tubal, or primary peritoneal cancer between May 2017 and September 2023 were initially enrolled from our hospital. However, 16 patients had prior exposure to PARP inhibitors during primary treatment, and 11 were lost to follow-up. Consequently, the study focused on 55 eligible patients. PFS was compared between patients receiving PARP inhibitor maintenance therapy and those who did not. Results: Among the 55 patients with PSR epithelial ovarian cancer, 18 received olaparib as maintenance therapy, 19 received niraparib, and 18 opted for observation. PARP inhibitor therapy significantly extended PFS (mean 24.0 months) compared to observation (mean 9.0 months, p = 0.0005), regardless of BRCA mutation status (HR = 0.20, 95% CI: 0.08–0.50). Subgroup analysis showed no statistical difference between olaparib and niraparib. Additionally, there was no PFS difference based on BRCA mutation status within both PARP inhibitor groups. Conclusion: Our retrospective study demonstrates that PARP inhibitor maintenance therapy, including olaparib and niraparib, significantly prolongs PFS in patients with PSR epithelial ovarian, tubal, or primary peritoneal cancer, These findings support the broad utilization of PARP inhibitors as a standard maintenance therapy for PSR epithelial ovarian cancer irrespective of BRCA mutation status. Summary: PARP inhibitor maintenance therapy, including olaparib and niraparib, significantly prolongs PFS in patients with PSR epithelial ovarian, tubal, or primary peritoneal cancer, irrespective of BRCA mutation status. PARP inhibitors can be recommended as a standard maintenance therapy for PSR epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Objectives: Numerous studies have investigated the predictive significance of the platelet-to-lymphocyte ratio (PLR) in oral squamous cell carcinoma(OSCC). However, the results of studies on its prognostic value remain controversial. This study aims to evaluate the prognostic significance of the PLR in patients with OSCC. Materials and methods: We conducted a comprehensive search of PubMed, Embase, the Cochrane Library, and Web of Science databases for all studies investigating the association between PLR and prognosis in OSCC, from the inception of each database up to November 2023. The outcome measures included overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS). To identify potential sources of heterogeneity, sensitivity and subgroup analyses were performed, alongside an assessment of publication bias. The analyses in this study were conducted using RevMan and Stata software. Results: According to the inclusion criteria, 20 articles were included, including 5,714 patients.The meta-analysis revealed that an elevated PLR adversely affects OS (HR = 1.58; 95% CI: 1.29–1.94; p < 0.0001), DFS (HR = 1.71; 95% CI: 1.20–2.42; p < 0.003), and DSS (HR = 2.41; 95% CI: 1.79–3.25; p < 0.00001). The results of the subgroup analysis showed that a preoperative high PLR was associated with reduced OS when the PLR threshold was ≤ 150 (HR = 1.49, P = 0.0003).When the PLR threshold was > 150, Preoperative PLR was not significantly associated with the prediction of overall survival (OS) in OSCC. (P > 0.05). Conclusion: The prognostic significance of PLR in patients with oral cancer is evident in terms of OS, DSS, and DFS. Nonetheless, it is crucial to note that the predictive value of PLR might depend on specific threshold values. [ABSTRACT FROM AUTHOR]

Purpose: Loddo et al. (Br J Cancer 100:959–70, 2009) established the prognostic significance of cell cycle markers and "Cell-Cycle Phenotypes" in breast carcinoma. This study aims to 1) identify prognostic cell-cycle markers in sarcoma, and 2) assess the prognostic potential of specific cell-cycle phenotypes in sarcoma. Methods: Tissue samples from 128 soft tissue sarcomas were stained for four cell cycle-specific markers: Mcm2, Geminin, Plk1, and H3S10ph. Only primary soft tissue tumors (liposarcoma, leiomyosarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma) were included in the analysis. Any tumor coming from a recurrent or metastatic lesion were excluded from the analysis. Three cell-cycle phenotypes (I, II, III) were derived from marker expression patterns. Prognostic significance was evaluated in a subset of primary soft tissue sarcomas using Cox regression for survival analysis. Results: Compared to phenotype I, the phenotype III tumors had a decreased 5-year overall survival (HR 6.81 [2.36–19.61]; p = < 0.001), 5-year disease-free survival (HR 1.07 (1.02–1.18); p = 0.004), and 5-year metastasis-free survival (HR 4.34 [1.58–11.93]; p = 0.004). High expression of Plk1 was associated with decreased 5-year overall survival (HR: 4.04 CI [1.21–6.67; p = 0.02) and 5-year metastasis-free survival (HR: 2.91 CI [1.15–7.37]; p = 0.03). Geminin was also found to have a decreased 5-year overall survival (HR:2.84 CI [1.21–6.67]; p = 0.02). No statistical difference in prognostication were noted between phenotypes and the AJCC system. Conclusions: We identified three unique sarcoma cell cycle phenotypes that have prognostic significance. This performs similarly to the AJCC staging system. [ABSTRACT FROM AUTHOR]

Objective: The efficacy of lymph node ratio (LNR) as a prognostic indicator in locally advanced gastric cancer (LAGC) patients underwent radical resection after neoadjuvant immunochemotherapy (NICT) remains to be demonstrated. The objective of the current retrospective study is to investigate the relationship between LNR and survival in patients with LAGC who underwent radical resection after NICT. Methods: A retrospective analysis was performed on 121 cases of LAGC in patients underwent radical resection after NICT between July 2020 and October 2023. The LNR values of the patients were divided into two groups using X-tile software. The first group, designated the low LNR group, comprised patients with LNR values of ≤ 33%. The second group, designated the high LNR group, comprised patients with LNR values of > 33%. The correlation between patient survival rates and a range of clinical and pathological variables was examined. Results: Overall, 121 patients were enrolled: 108 with low-LNR (LNR ≤ 33%) and 13 with high-LNR (LNR > 33%). A better 2-year overall survival (OS) (88.5% vs. 32.6%; p < 0.001) and progression-free survival (PFS) (80.2% vs. 23.5%; p < 0.001) were observed in patients with low LNR. A similar result was also found in those with non-pathological complete response group (non-pCR), where the 2-year OS was 87.2% vs. 32.6% (p < 0.001), and the 2-year PFS was 77.7% vs. 23.5% (p < 0.001). Compared to the pathologic lymph nodes staging (ypN), LNR exhibited similar prognostic capabilities for OS and PFS. Multivariate analysis indicated that LNR was an independent prognostic factor for both OS (HR 6.258, 95% CI 1.798–21.778; p = 0.004) and PFS (HR 3.431, 95% CI 1.341–8.780; p = 0.010), but not ypN. Conclusions: LNR may serve as a viable indicator for prognostication in LAGC patients treated with NICT. [ABSTRACT FROM AUTHOR]

Background: Exploration of novel combination mode of pyrotinib and chemotherapy for heavily pretreated HER2-positive metastatic breast cancer (MBC) and how to balance survival benefits and compliance are still urgent problems in clinical practice. The current single-arm prospective phase II study aimed to evaluate the efficacy and safety of pyrotinib in combination with metronomic oral etoposide in heavily pretreated HER2-positive MBC. Methods: HER2-positive MBC patients previously treated with trastuzumab were enrolled to receive oral pyrotinib 400 mg per day and metronomic oral etoposide 50 mg per day d1-21 every 28 days, until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), and safety. Results: 22 patients were enrolled with a median of 4 prior treatment regimens for MBC. During the follow-up of 20 evaluable patients, the median PFS was 9.0 months (95% CI, 7.6–10.4 months), and the median OS was 27.0 months (95%CI, 20.9–33.1 months). The ORR was 30% (6/20), the DCR was 80% (16/20), and the CBR was 65% (13/20). The most common grade 3 adverse events (AEs) included nausea (15%), vomiting (15%), diarrhea (5%), anemia (5%), and peripheral neuropathy (5%). No grade 4 or lethal AEs were observed. Conclusion: The combination of pyrotinib with metronomic oral etoposide has achieved promising clinical benefits in heavily pretreated HER2-positive MBC, with acceptable and manageable toxicity. Trial registration: Registry number: NCT03923179. Registered April 18, 2019. [ABSTRACT FROM AUTHOR]

Background: Pancreatic adenocarcinoma (PAC) is a disease of decimal prognosis, with around 50% of patients presenting with metastatic disease. Previous trials reported a high incidence of early onset pancreatic cancer (EOPAC) in Egypt, presenting about 25% of patients with PAC. The clinic-pathological features and prognosis of EOPAC needs more study. Patients and methods: A retrospective analysis of patients' records at Shefa Al-Orman comprehensive cancer center database. Patients with histo-pathologically confirmed diagnosis of PAC. We categorized patients according to the age at diagnosis into EOPAC (≤ 50 years) and average onset PAC (AOPAC). Data on risk factors, family history, presenting symptoms, clinic-pathological features, treatment, and prognosis were extracted. Patients with histopathologically confirmed diagnosis of pancreatic cancer diagnosed between December 2016-December 2022 were included. Results: The study cohort consisted of 412 patients. EOPAC represented 20.3% of patients, with no significant differences in risk factors and family history compared to AOPAC. Duration of symptoms before diagnosis is longer in EOPAC, with the majority of EOPAC presenting with localized disease (23.8%) and locally advanced tumors (28.5%) compared to AOPAC. AOPAC presented more with metastatic disease (64% vs. 45.2%, p = 0.003). EOPAC are usually submitted to more aggressive treatment including radical surgery, neoadjuvant therapy, and aggressive chemotherapy regimens in metastatic disease. Disease free survival (DFS) of EOPAC was shorter than AOPAC (11 months vs. 17 months, p = 0.889), but overall survival OS was significantly longer in EOPAC (10 months vs. 6 months, p = 0.013). Conclusion: Patients with EOPAC in Egypt represent around 25% of cases. EOPAC tend to have a shorter disease free survival (DFS) in patients presenting with localized disease. The overall survival (OS) is longer in EOPAC compared to AOPAC. Further studies are mandatory to identify the epidemiological and risk factors of EOPAC in Egypt. [ABSTRACT FROM AUTHOR]

The document is a correction notice for an article titled "PSMD9 promotes the malignant progression of hepatocellular carcinoma by interacting with c-Cbl to activate EGFR signaling and recycling." The correction addresses errors in Figures 1 and 6 of the original article, specifically related to plot type errors and mislabeling of fluorescence markers. The corrected figures provide data on the expression of PSMD9 in HCC tissues and its association with patient prognosis. The article is licensed under a Creative Commons Attribution 4.0 International License. [Extracted from the article]

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors that lacks effective treatment options. Cancer-associated fibroblasts (CAFs), an important component of the tumor microenvironment, associated with tumor progression, prognosis, and treatment response. This work aimed to explore the novel CAFs-associated target to improve treatment strategies in PDAC. Methods: The PDAC single-cell sequencing data (CRA001160, n = 35) were downloaded and integrated based on GSA databases to classify fibroblasts into fine subtypes. Functional enrichment analysis and coexpression regulatory network analysis were used to identify the functional phenotypes and biological properties of the different fibroblast subtypes. Fibroblast differentiation trajectories were constructed using pseudochronological analysis to identify initial and terminally differentiated subtypes of fibroblasts. The changes in the proportions of different fibroblast subtypes before and after PDAC immunotherapy were compared in responsive and nonresponding patients, and the relationships between fibroblast subtypes and PDAC immunotherapy responsiveness were determined based on GSA and GEO database. Using molecular biology methods to confirm the effects of BNIP3 on hypoxia and inflammation in CAFs. CAFs were co cultured with pancreatic cancer cells to detect their effects on migration and invasion of pancreatic cancer. Results: Single-cell data analysis divided fibroblasts into six subtypes. The differentiation trajectory suggested that BNIP3+ Fibro subtype exhibited terminal differentiation, and the expression of genes related to hypoxia and the inflammatory response increased gradually with differentiation time. The specific overexpressed genes in the BNIP3+ Fibro subtype were significantly associated with overall and disease progression-free survival in the patients with PDAC. Interestingly, the greater the proportion of the BNIP3+ Fibro subtype was, the worse the response of PDAC patients to immunotherapy, and the CRTL treatment regimen effectively reduced the proportion of the BNIP3+ Fibro subtype. After knocking out BNIP3, the hypoxia markers and inflammatory factors of CAFs were inhibited. Co-culture of CAFs with pancreatic cancer cells can increase the migration and invasion of pancreatic cancer, but this could be reversed by knocking out BNIP3. Conclusions: This study revealed the BNIP3+ Fibro subtype associated with hypoxia and inflammatory responses, which was closely related to the poor prognosis of patients with PDAC, and identified signature genes that predict the immunotherapy response in PDAC. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to develop nomograms for predicting outcomes following immunotherapy in patients diagnosed with intrahepatic cholangiocarcinoma (ICC). Patients and methods: A retrospective analysis was conducted on data from 75 ICC patients who received immunotherapy at Jinling Hospital and Drum Hospital. The discriminative power, accuracy, and clinical applicability of the nomograms were assessed using the concordance index (C-index), calibration curve, and decision curve analysis (DCA). The predictive performance of the nomograms for overall survival (OS) and progression-free survival (PFS) was evaluated using the area under the receiver operating characteristic (ROC) curve. Kaplan-Meier curves were also generated for validation purposes. Results: Multivariable analysis identified independent prognostic factors for OS, including CA19-9 levels, portal vein tumor thrombus (PVTT) grade, bifidobacteria administration, and surgery. The C-index of the nomogram for OS prediction was 0.722 (95% confidence interval [CI]: 0.661–0.783). Independent prognostic factors for PFS included CA19-9 levels, albumin, and bilirubin, with a C-index of 0.678 (95% CI: 0.612–0.743) for the nomogram predicting PFS. Calibration curves demonstrated strong concordance between predicted and observed outcomes, while DCA and Kaplan-Meier curves further supported the clinical utility of the nomogram. Conclusion: The nomogram developed in this study demonstrated favorable performance in predicting the prognosis of ICC patients undergoing immunotherapy. Additionally, our findings, for the first time, identified probiotics as a potential prognostic marker for immunotherapy. This prognostic model has the potential to enhance patient selection for immunotherapy and improve clinical decision-making. [ABSTRACT FROM AUTHOR]

Background: Some colorectal cancers (CRCs) are clinically diagnosed as cT4a with serosal invasion (SI). However, the cT4a is most often underdiagnosed pathologically as pT3 without SI by hematoxylin–eosin (H&E) staining alone. Using Elastica van Gieson (EVG) staining, some pT3 tumors invade the elastic lamina (EL), which extends just below the serosal layer. Recently, EL invasion (ELI) has been described as a poor prognostic factor for disease-free survival (DFS) and overall survival (OS) in patients with pStage II CRC. However, its clinicopathological significance remains unclear due to the limited number of studies and poor understanding of ELI. Objective: This study investigated the association between the ELI and patient prognosis. Methods: After 1982, pathological diagnosis was routinely performed using H&E and EVG staining methods, and long-term follow up was performed until 2016. All clinicopathological features including ELI were prospectively registered into our computer and 569 patients with pStage II CRC were collected from the database. Based on the ELI status, pT3 was divided into three pathological categories: pT3ELI − was defined as pT3a, pT3ELI + as pT3b and unidentified EL (pT3EL −) as pT3u. Results: Using H&E staining alone, gross cT4a was most often pathologically underdiagnosed as pT3 (93.8%) and very rarely as pT4a, resulting in a large diagnostic discrepancy. Using EVG staining, 60.7% of the cT4a tumors were diagnosed as pT3b. The 10-year DFS and OS rates were similar for pT3a and pT3u patients. However, the 10-year DFS and OS rates of pT3b patients were significantly lower than those of pT3a patients (75.6% vs. 95.6%, p < 0.0001 and 58.4% vs. 70.6%, p = 0.0024, respectively) but did not differ from those of pT4a patients (70.6%, p = 0.5799 and 52.0%, p = 0.1116, respectively). Multivariate analysis revealed that the ELI was the strongest independent risk factor for recurrence and CRC-specific death (p < 0.0001). Conclusions: A better understanding of the ELI allows us to reconsider the diagnostic discrepancy of serosal invasion, i.e., pT3b should be considered pT4a. The ELI-based subclassification of pT3 is expected to be incorporated into the TNM staging system in the future. The ELI is a notable prognostic indicator in patients with pStage II CRC. [ABSTRACT FROM AUTHOR]

Objective: Immune checkpoint inhibitor (ICI) therapy activates the immune system to recognize and eliminate cancer cells that have escaped surveillance. This study aimed to compare the treatment outcome of advanced and recurrent cervical cancer patients treated with first-line platinum and paclitaxel with or without ICI. Methods: Data from 69 advanced and recurrent cervical cancer patients treated with first-line ICI plus platinum and paclitaxel (N = 33) or first-line platinum and paclitaxel (N = 36) were reviewed between March 2020 and January 2023 in this retrospective study. Patients chose treatment based on the actual disease condition, patient willingness, and medical advice. Additionally, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were calculated, and adverse events were gained. Results: There was no difference in baseline data between patients receiving the two different treatments (all P > 0.05). Complete response rate (18.2% vs. 8.3%; P = 0.294), ORR (48.5% vs. 30.6%; P = 0.127), and DCR (81.8% vs. 72.2%; P = 0.345) tended to ascend in patients treated with ICI plus platinum and paclitaxel compared to those treated with platinum and paclitaxel, although there was no statistical significance. In patients treated with ICI plus platinum and paclitaxel, the median PFS was 10.3 months and the median OS was not reached. Meanwhile, the median PFS and OS were 7.7 and 16.9 months in patients treated with platinum and paclitaxel. PFS (P = 0.036) and OS (P = 0.033) were increased in patients treated with ICI plus platinum and paclitaxel versus those treated with platinum and paclitaxel, which was verified by multivariate Cox regression analyses (both P < 0.05). No difference was observed in the occurrence of adverse events between patients receiving the two different treatments (all P > 0.05). Conclusion: First-line ICI plus platinum and paclitaxel yields better treatment responses, longer survival, and non-differential adverse events versus first-line platinum and paclitaxel in advanced and recurrent cervical cancer patients. [ABSTRACT FROM AUTHOR]

Background: There are some changes in the new 9th edition Tumor-Node-Metastases (TNM) staging system for lung cancer, including subdividing M1c into M1c1 and M1c2 stage. The aim of this study was to assess the prognostic performance of the updated classification system and try to provide some real-world application data among advanced lung adenocarcinoma patients with bone metastases. Methods: Advanced lung adenocarcinoma patients in M1c stage with bone metastases who receiving first-line first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and T790M-guided osimertinib as the second-line therapy were retrospectively screened from December 2016 to December 2021. A total of 126 patients were enrolled in this study. 62 patients and 64 patients were subdivided into M1c1 and M1c2 groups according to the 9th edition of TNM staging system.The first-line real-world progression-free survival (1LrwPFS), the second-line real-world progression-free survival (2LrwPFS), post-progression survival (PPS) and real-world overall survival (rwOS) were analyzed. Results: The overall median rwOS was 40.1 months (95% CI 35.996–44.204). 1LrwPFS was 13.9 months (95% CI 12.653–15.147) and 2LrwPFS was 14.5 months (95% CI 11.665–17.335) for all patients.Patients in M1c2 stage was inferior to M1c1 stage patients in rwOS (35.2 months vs. 42.9 months, HR = 0.512, P = 0.005). 2LrwPFS was moderately correlated with rwOS (r = 0.621, R2 = 0.568, P = 0.000). Multivariate analysis showed performance status (PS) score ≥ 2 and TP53 alteration positive were independent prognostic factors of worse rwOS. Conclusions: More refined stratification of M1c according to the 9th edition of TNM staging system is conducive to the judgment of prognosis and the implementation of precision medicine for patients. [ABSTRACT FROM AUTHOR]

Background: Effective management of adverse events is required to maintain sufficient imatinib dosing when treating patients with gastrointestinal stromal tumors (GISTs). Skin rash is a common adverse event of imatinib, which can be effectively controlled by systemic steroid treatment without imatinib dose modification or interruption. However, the impact of the use of systemic steroids on the efficacy of imatinib treatment remains unclear. Methods: Between October 2014 and February 2022, 277 consecutive patients from a prospective registry of GIST patients were included as the study population. Patients who started systemic steroids due to grade ≥ 3 skin rash or grade 2 skin rash with grade 2 pruritis were classified as the steroid group, whereas patients who did not develop a skin rash or those who did not require steroids for a mild skin rash were classified as the control group. Efficacy outcomes were compared between the two groups. Results: Among the 277 patients, 30 (10.8%) were treated with systemic steroids for skin rash. There was no significant difference in progression free survival (PFS) or overall survival (OS) between the steroid and control groups (3-year PFS, 67.7% vs. 65.1%, p = 0.53; 3-year OS, 91% vs. 89.9%, p = 0.67, respectively). The use of systemic steroids was not an independent factor associated with PFS (hazard ratio 0.73, 95% confidence interval 0.36–1.49, p = 0.39) and OS (hazard ratio 0.37, 95% confidence interval 0.12–1.18, p = 0.09). In the steroid group, patients who successfully maintained the imatinib dosage showed a trend toward more favorable survival outcomes than those who did not (3-year PFS, 73.3% vs. 44.4%, p = 0.34; 3-year OS, 95.8% vs. 75.0%, p = 0.15, respectively). Conclusions: The use of systemic steroids for the control of imatinib induced severe skin rash did not adversely affect the efficacy outcomes of imatinib in patients with advanced GIST. [ABSTRACT FROM AUTHOR]

Objective: Our study tried to evaluate the prognostic utility of preoperative serum cyfra21-1 in patients with penile squamous cell carcinoma (PSCC). Methods: This retrospective study analyzed data from 94 patients who underwent either partial or radical penectomy accompanied by bilateral inguinal or pelvic lymphadenectomy at our institution from 2010 to 2018. The median duration of follow-up was 66.5 months. Serum cyfra21-1 concentrations were quantified through enzyme-linked immunosorbent assay, with patients classified into two groups based on cyfra21-1 levels (≤ 3.30 ng/ml and > 3.30 ng/ml). The impact of cyfra21-1 levels on clinical outcomes was evaluated. Results: Among the 94 patients, 68 (72.3%) had normal cyfra21-1 levels, while 26 (27.6%) exhibited elevated cyfra21-1 levels. During the follow-up period, 38 patients (40.4%) experienced relapse, and 35 patients (37.2%) died from PSCC. A significantly higher occurrence of advanced pathological grades was observed in the elevated cyfra21-1 group compared to the normal group (P = 0.029). Patients with elevated cyfra21-1 levels had significantly worse disease-free survival (DFS) and disease-specific survival (DSS) than those with normal levels (P < 0.001 and P < 0.001, respectively). In multivariate analysis, cyfra21-1 (HR: 3.938, 95% CI: 1.927–8.049, P < 0.001), lymph node involvement (HR: 8.277, 95% CI: 2.261–30.298, P = 0.001), pathological grade (HR: 2.789, 95% CI: 1.110–7.010, P = 0.029), and ECOG (Eastern Cooperative Oncology Group) performance status (HR: 1.751, 95% CI: 1.028–2.983, P = 0.039) were independent predictors of worse DFS. Similarly, CYFRA 21 − 1 (HR: 3.000, 95% CI: 1.462–6.156, P = 0.003), lymph node involvement (HR: 9.174, 95% CI: 2.010–41.862, P = 0.003), and ECOG performance status (HR: 1.856, 95% CI: 1.053–3.270, P = 0.032) were independent predictors of worse DSS. Conclusions: High preoperative serum cyfra21-1 levels correlate with greater tumor aggressiveness and represent a novel, effective, and convenient prognostic biomarker for PSCC. [ABSTRACT FROM AUTHOR]

Background: Retroperitoneal dedifferentiated liposarcoma is associated with a high risk of recurrence; however, treatment strategies that are more effective than surgery remain to be established. This study aimed to determine the optimal number of surgeries that would be effective for patients with recurrent disease. Furthermore, the improvement in prognosis was evaluated according to the malignancy level. Methods: The effect of each type of surgery on the prognosis of 118 patients with retroperitoneal dedifferentiated liposarcoma treated at the Osaka International Cancer Institute between 1997 and 2022 was investigated. Among the 118 patients, 103 underwent initial surgery, while 54 and 30 patients underwent second and third surgeries, respectively. The overall and disease-free survival rates of each group were compared using the Kaplan–Meier method, and the log-rank test was used to determine statistical significance in univariate analysis. 18F-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) was used to assess malignancy. Maximum standardized uptake values (SUVmax) of ≥ 4 and < 4 were classified as high and low malignancy, respectively. Results: The first and second surgeries resulted in a significant improvement in the overall survival rate, regardless of the malignancy level (p < 0.001); however, no significant improvement in prognosis was observed after the third surgery (p = 0.077). Low-grade malignancies are associated with a better postoperative prognosis, even in cases of recurrence. In contrast, high-grade malignancies exhibit a reduction in surgical efficacy. Conclusions: This study highlights the importance of considering the tumor malignancy level and the patient's overall condition when deciding whether to perform repeated surgical interventions. Surgical treatment can prolong overall survival, even in patients with recurrence; however, it is advisable to assess malignancy levels when determining the suitability of surgery beyond the second recurrence. [ABSTRACT FROM AUTHOR]

Background: Muscle invasive bladder cancer (MIBC) treatment combines systemic therapy and radical cystectomy (RC) or local (chemo-)radiotherapy. Response to systemic therapy is an important outcome predictor but is difficult to assess pre-operatively. Methods: We analyzed multiparametric MRI (mpMRI) in consecutive MIBC patients receiving cisplatin-based neo-adjuvant chemotherapy at our institution. Two readers, blinded for pathological outcome, independently scored mpMRI before and after 2 and 4 cycles using both a qualitative 3-step method and nacVI-RADS. We analyzed accuracy of mpMRI scores to predict pathologic complete response (pCR) and inter-observer agreement. Results: We analyzed 46 patients receiving NAC, 6 patients did not undergo RC after NAC and were excluded. Eleven out of 40 (28%) patients showed a pCR. mpMRI could be assessed in over 90% of patients. Radiologic complete response (rCR) using both methods was significantly associated with pCR, with an overall specificity of 96% and sensitivity of 36% and a high inter-observer agreement. rCR as assessed by the 3-step score was significantly associated with disease free survival (DFS) benefit. Conclusion: The use of nacVI-RADS can predict pCR after NAC with high specificity but low sensitivity and a high inter-observer agreement. A 3-step score adds value in determining local residual disease, rCR assessed by this method could correlate with DFS benefit. mpMRI scores should be prospectively assessed in future trials of multimodal management of MIBC and can be a predictive asset in routine clinical management. [ABSTRACT FROM AUTHOR]

Background: Bidirectional crosstalk between HER2 and estrogen receptor (ER) pathways may influence outcomes and the efficacy of endocrine therapy (ET). Low HER2 expression levels (HER2-low) have emerged as a predictive biomarker in patients with breast cancer (BC). Methods: PALLAS is an open, international, phase 3 study evaluating the addition of palbociclib for 2 years to adjuvant ET in patients with stage II-III ER-positive/HER2-negative BC. To assess the impact of HER2 expression on patient outcomes in the phase III PALLAS trial, we analyzed (1) the association between rate of HER2-low with demographic and clinicopathological parameters, (2) the prognostic value of HER2-low status on invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS) and (3) HER2 expression's value as a predictive biomarker of response to palbociclib. HER2-low was defined as HER2 immunohistochemistry (IHC) 1 + or IHC 2 + with negative in situ hybridization (ISH). All pathologic evaluation was performed locally. Prognostic and predictive power of HER2 were assessed with Cox models. Results: From the original PALLAS intention-to-treat population (N = 5753), 5304 patients (92.2%) were included in this analysis. Among these, 2254 patients (42.5%) were classified as having HER2 IHC 0 (HER2-0), and 3050 (57.5%) as having HER2-low disease (1838 with IHC 1 + and 1212 with IHC 2 +). Median follow-up was 59.8 months. HER2-low prevalence varied significantly across 21 participating countries (range 16.7% to 75.6%; p < 0.001) and was more frequent in patients enrolled in North America (63.1%) than in Europe (53.4%) or other regions (53.4%) (p < 0.001). HER2 status was not significantly associated with iDFS in a multivariable Cox model (hazard ratio 0.93, 95% confidence interval 0.81 – 1.06). No significant interaction was observed between treatment arm and HER2 status for iDFS (p = 0.43). Similar results were obtained for DRFS and OS. Conclusions: In this large, prospective, global patient cohort, no differences were observed in clinical parameters, prognosis, or differential benefit from palbociclib between HER2-0 and HER2-low tumors. Significant geographic variability was observed in the prevalence of HER2-low status, suggesting a high degree of variation in pathologic assessment of HER2 expression without impact on outcomes. [ABSTRACT FROM AUTHOR]

Glypican-3 (GPC-3) is predominantly found in the placenta and fetal liver, with limited expression in adult tissues. Its re-expression in hepatocellular carcinoma (HCC) and secretion into the serum highlights its potential as a diagnostic marker. GPC-3 is involved in important cellular processes such as proliferation, metastasis, apoptosis, and epithelial–mesenchymal transition through various signaling pathways including Wnt, IGF, YAP, and Hedgehog. To review the structure, biosynthesis, and post-translational modifications of GPC-3, and to elucidate its signaling mechanisms and role as a pro-proliferative protein in HCC, emphasizing its diagnostic and therapeutic potential. A comprehensive literature review was conducted, focusing on the expression of GPC-3 in various tumors, with a special emphasis on HCC. The review synthesized findings from experimental studies and clinical trials, analyzing the overexpression of GPC-3 in HCC, its differentiation from other liver diseases, and its potential as a diagnostic and therapeutic target. GPC-3 overexpression in HCC is linked to aggressive tumor behavior and poor prognosis, including shorter overall and disease-free survival. Additionally, GPC-3 has emerged as a promising therapeutic target. Ongoing investigations, including immunotherapies such as monoclonal antibodies and CAR-T cell therapies, demonstrate potential in inhibiting tumor growth and improving clinical outcomes. The review details the multifaceted roles of GPC-3 in tumorigenesis, including its impact on tumor-associated macrophages, glucose metabolism, and epithelial–mesenchymal transition, all contributing to HCC progression. GPC-3's re-expression in HCC and its involvement in key tumorigenic processes underscore its value as a biomarker for early diagnosis and a target for therapeutic intervention. Further research is warranted to fully exploit GPC-3's diagnostic and therapeutic potential in HCC management. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the survival outcomes of transarterial chemoembolization (TACE) between patients with early recurrent hepatocellular carcinoma (rHCC) after hepatic resection, stratified by cytokeratin (CK) 19 expression. Methods: A retrospective analysis was conducted on 63 patients with early rHCC after hepatic resection who underwent TACE between January 2017 and December 2021. Patients were divided into two groups based on CK19 expression: CK19-negative (n=31) and CK19-positive (n=32). Overall survival (OS) and progression-free survival (PFS) were compared between the two groups using the Kaplan-Meier method and log-rank test. Cox regression analysis was performed to identify independent risk factors for OS and PFS. Results: The CK19-negative group demonstrated a significantly longer median OS compared to the CK19-positive group (635 days vs. 432 days, p=0.013). Similarly, the CK19-negative group had a longer median PFS than the CK19-positive group (291 days vs. 117 days, p=0.014). Multivariate Cox analysis identified Child-Pugh A grade, CK19-negative expression, and increased TACE sessions as protective factors for OS. No severe TACE-related adverse events were observed. Conclusion: In patients with early rHCC after hepatic resection, those with CK19-positive expression had poorer survival outcomes following TACE compared to CK19-negative patients. These findings suggest the need for additional therapies to improve survival in CK19-positive individuals. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to use propensity score matching (PSM) to explore the long-term outcomes and failure patterns in locally advanced rectal cancer (LARC) patients with positive versus negative lateral pelvic lymph node (LPLN). Materials and methods: Patients with LARC were retrospectively divided into LPLN-positive and LPLN-negative groups. Clinical characteristics were compared between the groups using the chi-square test. PSM was applied to balance these differences. Progression-free survival (PFS) and overall survival (OS), and local–regional recurrence (LRR) and distant metastasis (DM) rates were compared between the groups using the Kaplan–Meier method and log-rank tests. Results: A total of 651 LARC patients were included, 160 (24.6%) of whom had positive LPLN and 491 (75.4%) had negative LPLN. Before PSM, the LPLN-positive group had higher rates of lower location (53.1% vs. 43.0%, P = 0.025), T4 stage (37.5% vs. 23.2%, P = 0.002), mesorectal fascia (MRF)-positive (53.9% vs. 35.4%, P < 0.001) and extramural venous invasion (EMVI)-positive (51.2% vs. 27.2%, P < 0.001) disease than the LPLN-negative group. After PSM, there were 114 patients for each group along with the balanced clinical factors, and both groups had comparable surgery, pathologic complete response (pCR), and ypN stage rates. The median follow-up was 45.9 months, 3-year OS (88.3% vs. 92.1%, P = 0.276) and LRR (5.7% vs. 2.8%, P = 0.172) rates were comparable between LPLN-positive and LPLN-negative groups. Meanwhile, despite no statistical difference, 3-year PFS (78.8% vs. 85.9%, P = 0.065) and DM (20.4% vs. 13.3%, P = 0.061) rates slightly differed between the groups. 45 patients were diagnosed with DM, 11 (39.3%) LPLN-positive and 3 (17.6%) LPLN-negative patients were diagnosed with oligometastases (P = 0.109). Conclusions: Our study indicates that for LPLN-positive patients, there is a tendency of worse PFS and DM than LPLN-negative patients, and for this group patients, large samples are needed to further confirm our conclusion. [ABSTRACT FROM AUTHOR]

Introduction: Anaplastic meningiomas, categorized as WHO grade 3 tumors, are rare and highly aggressive, accounting for 1-2% of all meningioma cases. Despite aggressive treatment, including surgery and Radiation, they exhibit a high recurrence rate and poor survival outcomes. The aggressive histopathological features emphasize the urgent need for effective management strategies. Methods: A retrospective multi-institutional analysis was conducted on patients with recurrent anaplastic meningioma who underwent re-irradiation between 2017 and 2023. Clinical, dosimetric, and outcome data were collected and analyzed, focusing on local control, progression free survival and treatment-related adverse events. Results: Thirty-four cases were analyzed, with a median follow-up 11 months after re-irradiation. Progression-free survival at 12 months was 61.9%, with higher doses correlating with better outcomes. Concomitant Bevacizumab improves progression-free survival and reduces the risk of radiation necrosis. CDKN2A homozygote deletion correlated with a higher risk of local failure. Symptomatic radiation necrosis occurred in 20.5% of cases, but its incidence was lower with concomitant Bevacizumab treatment. Conclusion: Re-irradiation presents a viable option for recurrent anaplastic meningioma despite the associated risk of radiation necrosis. Higher doses with concomitant Bevacizumab improve clinical outcomes and reduce toxicity. Individualized treatment approaches are necessary, emphasizing the importance of further research to refine management strategies for this challenging disease. [ABSTRACT FROM AUTHOR]

Immunotherapy with anti-PD-1 antibodies significantly improved the prognosis in advanced melanoma patients, but most of them develop primary or secondary resistance to the treatment. In this study, we evaluated efficacy and safety of a chemotherapy regimen with weekly carboplatin plus paclitaxel (wCP) in patients previously treated with anti-PD-1 antibodies. We retrospectively identified 30 patients with advanced melanoma treated at our Institute over the last eight years with wCP. The co-primary endpoints of the study were overall survival (OS) and progression-free survival (PFS). In addition, we evaluated treatment tolerability. For this patient cohort, median PFS and OS were 3.25 and 7.69 months, respectively. All included patients had previously received anti-PD-1 immunotherapy, most of them had ECOG PS 0–1, and only 5 patients had a BRAF V600 mutation. In univariable analysis, we observed shorter OS in patients with > 2 involved metastatic sites, superficial spreading histology, and serum lactate dehydrogenase (LDH) values above the median. Liver metastases were associated with worse outcomes, while radiotherapy treatment of brain metastases was associated with improved OS. However, in a multivariable Cox regression model, only LDH above the median, superficial spreading histology, and female sex were significantly associated with worse OS. We reported grade 3 and 4 treatment-related toxicities in 4 and 0 patients, respectively. In conclusion, chemotherapy with wCP is a valid palliative treatment in advanced melanoma who progressed with anti-PD-1 antibodies. [ABSTRACT FROM AUTHOR]

Objective: We explored the preliminary value of abnormal spindle-like microcephaly- associated (ASPM) protein in aiding precise risk sub-stratification, prediction of metabolic heterogeneity, and prognosis of neuroblastoma (NB). Methods: This retrospective study enrolled newly diagnosed patients with NB who underwent positron emission tomography/computed tomography (PET/CT) before therapy, and tumor tissue was collected after surgery. Regression analysis was used to evaluate ASPM expression and risk stratification in patients with NB. The expression levels of ASPM, clinical information, and PET/CT text features were analyzed using univariate and multivariate survival analyses. Finally, a correlation analysis was used to explore the relationship between ASPM and tumor metabolic heterogeneity. Results: There were 48 patients with NB in this study (35 boys and 13 girls); 22 patients progressed and 16 died. We found that the level of ASPM was highly associated with risk stratification (OR = 5.295, 95%IC: 1.348–41.722, p = 0.021). Patients with NB and high-risk stratification with high ASPM level had a lower 3-year progression-free survival (PFS) rate (14.28%) and 1-year PFS rate (57.14%) than those with low ASPM level (57.14% and 93.75%, respectively). Using univariate and multivariate survival analyses, this study revealed that ASPM and LDH were independent risk factors for both PFS and overall survival (OS), whales GLZLM_ZLNU was only a risk factor for PFS. Conclusion: ASPM holds promise as a novel biomarker for refining current risk stratification and predicting prognosis in neuroblastoma. Elevated levels of ASPM, LDH, and GLZLM_ZLNU may be associated with poorer survival outcomes in neuroblastoma patients. [ABSTRACT FROM AUTHOR]