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BACKGROUND: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolonged life in patients with metastatic castration-resistant prostate cancer (mCRPC) in VISION (NCT03511664). However, distinguishing between patients likely and unlikely to respond remains a clinical challenge. We present the first multivariable models of outcomes with 177Lu-PSMA-617 built using data from VISION, a large prospective phase 3 clinical trial powered for overall survival. METHODS: Adults with progressive post androgen receptor pathway inhibitor and taxane prostate-specific membrane antigen (PSMA)-positive mCRPC received 177Lu-PSMA-617 plus protocol-permitted standard of care (SoC) or SoC alone. In this post hoc analysis, multivariable Cox proportional hazards models of overall survival (OS) and radiographic progression-free survival (rPFS), and a logistic regression model of prostate-specific antigen response (≥50% decline; PSA50) were constructed and evaluated using C-index or receiver operating characteristic (ROC) analyses with bootstrapping validation. Nomograms were constructed for visualisation. FINDINGS: Patients were randomised between June 2018 and October 2019. Data from all 551 patients in the 177Lu-PSMA-617 arm were analysed in multivariable modelling. The OS nomogram (C-index, 0.73; 95% confidence interval [CI], 0.70-0.76) included whole-body maximum standardised uptake value (SUVmax), time since diagnosis, opioid analgesic use, aspartate aminotransferase, haemoglobin, lymphocyte count, presence of PSMA-positive lesions in lymph nodes, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and neutrophil count. The rPFS nomogram (C-index, 0.68; 0.65-0.72) included SUVmax, time since diagnosis, opioid analgesic use, lymphocyte count, presence of liver metastases by computed tomography, LDH, and ALP. The PSA50 nomogram (area under ROC curve, 0.72; 95% CI, 0.68-0.77) included SUVmax, lymphocyte count and ALP. Performances of the OS and rPFS models were maintained when they were reconstructed excluding SUVmax. INTERPRETATION: These models of outcomes with 177Lu-PSMA-617 are the first built using prospective phase 3 data. They show that a combination of pretreatment laboratory, clinical, and imaging parameters, reflecting both patient and tumour status, influences outcomes. These models are important for aiding treatment selection, patient management, and clinical trial design. FUNDING: Novartis.

BackgroundImmune checkpoint inhibitor (ICI) therapies have become increasingly popular treatment options for patients with cancer, even for patients in non-metastatic settings. Survival and responses have been reported for individual tumor types, but little is known about these outcomes, collectively. We sought to provide an overview of overall survival (OS) and progression-free survival (PFS) in ICI drugs tested in registration trials.MethodsIn a cross-sectional analysis of US FDA oncology ICI drug approvals (2011-2023), we searched for supporting ICI registration trials. We characterized these trials, regarding differences in median OS and PFS between patients in intervention and control arm participants in ICI registration trials; percentage of patients who receive ICI crossover; and whether there is correlation between the percentage of crossover and differences in OS or PFS.ResultsFifty-six (54.4 %) approvals had trials that reported median OS for both intervention and control arms (median difference was 2.8 months; IQR: 2.2 to 5.0 months). Sixty-five (63.1 %) approvals had trials that reported PFS data for both arms (median of 0.9 months; IQR: -0.2 to 3.0 months). Subsequent therapy was common (median=18.9 %) and was significantly correlated with a higher difference in median OS in all studies with reported differences (R2 =0.15; p = 0.001).ConclusionICIs are increasingly used in the treatment of cancer, yet the median OS improvement is modest, and many ICIs have not been tested for OS benefit. OS is the outcome most meaningful for patients, and drug regulation should require better testing and reporting of these data.

BACKGROUND: In the phase 3 EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 study, cemiplimab significantly improved overall survival (OS) versus chemotherapy for patients with recurrent or metastatic cervical cancer who progressed after first-line platinum-based chemotherapy. We present a post hoc subgroup analysis of patients enrolled in Japan. METHODS: Patients were enrolled regardless of programmed cell death-ligand 1 status and randomized 1:1 to cemiplimab 350 mg intravenously every 3 weeks or investigators choice  single-agent chemotherapy for up to 96 weeks. Primary endpoint was OS. Key secondary endpoints were progression-free survival (PFS) and objective response rate (ORR). RESULTS: Overall, 608 patients were randomized, of whom 56 (9.2%) were in Japan (cemiplimab, n = 29; chemotherapy, n = 27). The median (range) duration of follow-up was 13.6 (6.0-25.3) versus 18.2 (6.0-38.2) months for patients in Japan and for the overall population, respectively. Median OS (95% confidence interval [CI]) was 8.4 (7.0-not evaluable) and 9.4 (5.4-14.9) months for cemiplimab versus chemotherapy (hazard ratio [HR]: 0.86; 95% CI: 0.43-1.68). Median PFS (95% CI) was 4.0 (1.4-8.2) versus 3.7 (1.8-4.2) months with cemiplimab and chemotherapy (HR: 0.90; 95% CI: 0.50-1.61), respectively. ORR was 17.2% for cemiplimab and 7.4% for chemotherapy (odds ratio, 2.47; 95% CI, 0.44-13.99). Incidence of treatment-emergent adverse events at any grade was 79.3% for cemiplimab and 100% for chemotherapy. Grade ≥3 adverse events were 37.9% versus 66.7% with cemiplimab and chemotherapy, respectively. DISCUSSION: While acknowledging limitations inherent to a small subgroup analysis, the HR of 0.86 observed in Japanese patients suggests an emerging survival benefit despite a 4.6-month shorter median duration of follow-up versus the overall study population.

While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy (PRINCE, NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.0010) but not G12V (p = 0.7101), even with adjustment for clinical covariates. Early, on-therapy clearance of G12D (p = 0.0002), but not G12V (p = 0.4058), strongly associates with OS for PRINCE. Similar results are obtained for the SOC cohort, and for PFS in both cohorts. These results suggest ctKRAS G12D but not G12V as a promising prognostic biomarker for mPDAC and that G12D clearance could also serve as an early biomarker of response.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Sacituzumab govitecan (SG), a first-in-class anti-trophoblast cell surface antigen 2 (Trop-2) antibody-drug conjugate, demonstrated superior efficacy over single-agent chemotherapy (treatment of physicians choice [TPC]) in patients with metastatic triple-negative breast cancer (mTNBC) in the international, multicenter, phase III ASCENT study.Patients were randomly assigned 1:1 to receive SG or TPC until unacceptable toxicity/progression. Final efficacy secondary end point analyses and post hoc analyses of outcomes stratified by Trop-2 expression and human epidermal growth factor receptor 2 status are reported. Updated safety analyses are provided.In this final analysis, SG (n = 267) improved median progression-free survival (PFS; 4.8 v 1.7 months; hazard ratio (HR), 0.41 [95% CI, 0.33 to 0.52]) and median overall survival (OS; 11.8 v 6.9 months; HR, 0.51 [95% CI, 0.42 to 0.63]) over TPC (n = 262). SG improved PFS over TPC in each Trop-2 expression quartile (n = 168); a trend was observed for improved OS across quartiles. Overall, SG had a manageable safety profile, with ≤5% of treatment-related discontinuations because of adverse events and no treatment-related deaths. The safety profile was consistent across all subgroups.These data confirm the clinical benefit of SG over chemotherapy, reinforcing SG as an effective treatment option in patients with mTNBC in the second line or later.

Aim: To outline the demographic and clinical features, treatment approaches and clinical outcomes of patients treated with palbociclib as the initial therapy for HR+/HER2- advanced or metastatic breast cancer (aBC/mBC) in private healthcare facilities in Brazil. Materials & methods: This study involved a retrospective review conducted from June 2022 to May 2023. Results: The study included 121 patients, with an average age of 54.4 years, and 82 (67.7%) were menopausal at the time of diagnosis. Of these, 51 patients (42.1%) were treated with palbociclib and fulvestrant, while 67 patients (55.8%) received palbociclib and aromatase inhibitors. Most patients (65.3%) did not need to adjust their doses. The progression-free survival rates were 78% at 6 months and 60% at 12 months. Overall survival rates were 86% at 6 months and 70% at 12 months. Conclusion: Palbociclib combinations show promising effectiveness in managing HR+/HER2- advanced or metastatic breast cancer. Plain Language Summary Treatment & results in Brazilian women with advanced or metastatic breast cancer given palbociclib Breast cancer is a major health issue worldwide, and it is the most common cancer among women in Brazil, with death rates on the rise. A significant portion of breast cancer cases are hormone receptor-positive (HR+) and HER2-negative (HER2-), making targeted treatments essential. One such treatment is palbociclib, a medication that inhibits Cyclin-dependent kinase 4 and 6 (CDK4/6), enzymes important in cell division. Clinical trials such as PALOMA-1, PALOMA-2 and PALOMA-3 have shown that palbociclib can help patients with advanced or metastatic HR+/HER2- breast cancer live longer without their disease getting worse. Studies in real-world settings around the world have confirmed these benefits, evaluating how well the treatment works over time. Palbociclib was approved for use in Brazil in 2018. This study looks back at the records of women treated with palbociclib in private healthcare settings in the country. It aims to provide crucial information which can help guide future treatment decisions. Article highlights Breast cancer is a leading cause of cancer-related deaths among females worldwide, with Brazil reporting around 66,000 new cases and over 16,000 deaths in 2017, making it the most prevalent neoplasm affecting women across all regions of the country. Palbociclib, a first-in-class CDK4/6 inhibitor, has shown significant efficacy in clinical trials for HR+/HER2- advanced/metastatic breast cancer, demonstrating improved progression-free survival rates in the PALOMA-1, PALOMA-2 and PALOMA-3 trials. This study aims to describe the demographics, clinical attributes, treatment patterns and outcomes of Brazilian women receiving palbociclib as a first-line treatment for HR+/HER2- advanced/metastatic breast cancer in private healthcare institutions, following its approval in Brazil in February 2018. Data was collected from 13 study sites across Brazil between 2 June 2022 and 2 May 2023, with variables including patient demographics, clinical and tumor characteristics, early treatment history and detailed documentation of palbociclib combination treatment and its outcomes. Palbociclib combinations exhibit favorable effectiveness, as measured by progression-free survival and overall survival rates. Discontinuation rates were low, suggesting that these combinations are well-tolerated in the real-world setting. [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]

Objective: Hec1 is a component of the Ndc80 kinetochore complex and is frequently upregulated in various cancers. However, the clinical significance of Hec1 in cervical cancer remains largely unknown. This study aimed to investigate the expression patterns of Hec1 in cervical cancer and its relationship with the clinicopathological characteristics of patients diagnosed with the disease. Methods: Immunohistochemistry was used to assess the expression of Hec1 in 136 cervical cancer tissue samples and 82 normal cervical tissue samples. The relationship between Hec1 protein expression and the clinicopathological characteristics of cervical cancer patients was analyzed using the Chi-square test. Additionally, the association between Hec1 protein expression and patient survival was examined using Kaplan-Meier survival curves. Independent risk factors affecting the prognosis of cervical cancer patients were analyzed using the Cox proportional hazards regression model. Results: The positive expression rate of Hec1 protein in cervical cancer tissues was 83.82%, significantly higher than the 7.31% in normal cervical tissues. Compared to patients with negative Hec1 expression, those with positive expression exhibited significantly higher FIGO staging, increased lymph node metastasis, greater depth of tumor stromal infiltration, and larger tumor diameter. Multivariable analysis using the Cox proportional hazards regression model indicated that Hec1 positive expression was an independent risk factor for both overall survival (HR = 2.79, 95% CI: 1.65–4.05, p = 0.012) and progression-free survival (HR = 1.81, 95% CI: 1.22-3.18, p = 0.002) in cervical cancer patients. Kaplan-Meier survival curve analysis showed that patients with positive Hec1 expression experienced a lower overall survival (HR: 2.72, 95% CI: 1.15–4.52, p = 0.004) and progression-free survival (HR: 3.12, 95% CI: 1.62–5.03, p = 0.002) when compared to those with negative Hec1 expression. Conclusion: Hec1 is significantly upregulated in cervical cancer tissues and associated with poor prognosis in cervical cancer patients. Therefore, Hec1 could be a novel biomarker, not only for the diagnosis and treatment evaluation of cervical cancer but also as an indicator for predicting the prognosis of cervical cancer patients. [ABSTRACT FROM AUTHOR]

Background: For patients with advanced non‐small cell lung cancer (NSCLC) who have received frontline immunochemotherapy, subsequent treatment options are limited. As the first dual programmed cell death‐1 (PD‐1)/cytotoxic T lymphocyte‐associated antigen‐4 bispecific antibody approved globally, cadonilimab demonstrated potential antitumor activity in advanced NSCLC patients resistant to anti‐PD‐1/PD‐L1 antibodies. Methods: We retrospectively collected efficacy and safety data from advanced NSCLC patients treated with cadonilimab‐based regimens in later therapy lines. Results: A total of 41 advanced NSCLC patients refractory to anti‐PD‐1/PD‐L1 therapy were enrolled. More than half of the patients received cadonilimab‐based regimen as a fourth or later line of treatment. At the data cutoff date, treatment efficacy could be evaluated in 23 patients. One patient (4.3%) achieved partial response, eight patients (34.8%) experienced stable disease, and 14 patients (60.9%) progressed. The objective response rate and disease control rate were 4.3% and 39.1%, respectively. The median progression‐free survival for all evaluated patients was 108.0 days. Due to the short follow‐up period, the median overall survival has not yet been reached. Treatment‐related adverse events (TRAEs) and immune‐related AEs occurred in 63.4% and 22% patients, respectively. The most common TRAEs included gamma‐glutamyl transferase elevation (17.1%), coughing (14.6%), and fatigue (12.2%). Five patients (12.2%) experienced grade ≥3 TRAEs. Conclusions: In this heavily pretreated cohort of advanced NSCLC patients, cadonilimab‐based regimens showed moderate antitumor efficacy with a generally tolerable and manageable safety profile. However, more evidence is needed to support the administration of cadonilimab in NSCLC patients refractory to previous anti‐PD‐1/PD‐L1 therapy. [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]

Limited data exist on the effects of induction treatment in patients with newly diagnosed multiple myeloma (NDMM) and renal impairment (RI), who may also be ineligible for autologous stem cell transplant. This analysis investigated the impact of lenalidomide-bortezomib-dexamethasone (RVd) induction on renal function in patients from the Connect® MM Registry based on transplant status. Eligible patients were aged ≥18 years with symptomatic MM diagnosed ≤2 months before enrollment. Patients in this analysis received front-line RVd for ≥3 cycles and were grouped by transplant status and baseline renal function. As of August 4, 2021, 344 transplanted and 289 non-transplanted patients had received RVd for ≥3 cycles at induction. Improved renal function was observed at 3, 6, and 12 months in patients with all severities of RI at baseline. In patients with >60 and ≤60 creatinine clearance mL/min at baseline, median progression-free survival was 49.4 months and 47.6 months in transplanted patients and 35.7 months and 29.1 months in non-transplanted patients, respectively. These results provide real-world evidence that patients with NDMM and RI who receive front-line RVd for ≥3 cycles may have improved renal function regardless of transplant status, with renal function no longer affecting the long-term outcome. Clinical trial information: NCT01081028. [ABSTRACT FROM AUTHOR]

Background: Peritumoral brain edema (PTBE) represents a characteristic phenotype of intracranial gliomas. However, there is a lack of consensus regarding the prognosis and mechanism of PTBE. In this study, clinical imaging data, along with publicly available imaging data, were utilized to assess the prognosis of PTBE in glioblastoma (GBM) patients, and the associated mechanisms were preliminarily analyzed. Methods: We investigated relevant imaging features, including edema, in GBM patients using ITK-SNAP imaging segmentation software. Risk factors affecting progression-free survival (PFS) and overall survival (OS) were assessed using a Cox proportional hazard regression model. In addition, the impact of PTBE on PFS and OS was analyzed in clinical GBM patients using the Kaplan–Meier survival analysis method, and the results further validated by combining data from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). Finally, functional enrichment analysis based on TCIA and TCGA datasets identified several pathways potentially involved in the mechanism of edema formation. Results: This study included a total of 32 clinical GBM patients and 132 GBM patients from public databases. Univariate and multivariate analyses indicated that age and edema index (EI) are independent risk factors for PFS, but not for OS. Kaplan–Meier curves revealed consistent survival analysis results between IE groups among both clinical patients and TCIA and TCGA patients, suggesting a significant effect of PTBE on PFS but not on OS. Furthermore, functional enrichment analysis predicted the involvement of several pathways related mainly to cellular bioenergetics and vasculogenic processes in the mechanism of PTBE formation. While these novel results warrant confirmation in a larger patient cohort, they support good prognostic value for PTBE assessment in GBM. Conclusions: Our results indicate that a low EI positively impacts disease control in GBM patients, but this does not entirely translate into an improvement in OS. Multiple genes, signaling pathways, and biological processes may contribute to the formation of peritumoral edema in GBM through cytotoxic and vascular mechanisms. [ABSTRACT FROM AUTHOR]

Background: Sinonasal squamous cell carcinoma (SCC) is a rare disease entity, comprising less than 5% of malignancies of the head and neck. While surgery is the primary treatment approach, neoadjuvant and adjuvant therapies play crucial roles in enhancing the prognosis of patients undergoing treatment with the goal of cure. In this study, we aimed to explore the treatment outcomes of neoadjuvant chemotherapy (NAC) in patients with locally advanced sinonasal SCC. Methods: Medical records of patients diagnosed of locally advanced (cT3-4b, N0-3) sinonasal SCC treated with a definitive aim between January 2005 and March 2023 were retrospectively reviewed. Patients were categorized into the following groups based on the initial treatment: NAC followed by surgery, NAC followed by concurrent chemoradiotherapy (CCRT), definitive CCRT, or upfront surgery. Initial treatment plan was decided by a multidisciplinary team. Primary endpoint was overall survival (OS) and objective response rate, and secondary endpoints were progression free survival (PFS), cumulative incidence of local and distant failures, and treatment-related toxicity. The treatment response was assessed according to the RECIST criteria. Results: Total 126 patients were included, and the median follow-up period was 25.6 months. The objective response rate to NAC was 48.2%. The subsequent resection rate was 70%, 42.9%, and 16.7% for patients with stage T3, T4a, and T4b disease, respectively. Two-year progression-free survival did not differ significantly between the NAC followed by surgery and upfront surgery groups (53.6% vs. 60.6%, P = 0.615) or between the NAC followed by CCRT and definitive CCRT groups (26.7% vs. 37.4%, P = 0.506). Conclusion: NAC may be a valuable treatment option for patients with locally advanced sinonasal SCC, as it provides an opportunity for curative surgery and exhibits non-inferior oncological outcomes compared with upfront definitive local treatments. [ABSTRACT FROM AUTHOR]

Ovarian cancer is one of the most common gynecological malignancies. The current first-line treatment strategies for advanced ovarian cancer include surgery, chemotherapy, and maintenance therapy. Bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi) are primary maintenance treatments for advanced ovarian cancer. Previously, many patients declined these therapies before medicare coverage because of high costs. Bevacizumab and apatinib are anti-tumor angiogenic agents. In this case study, we describe a patient with advanced ovarian cancer who underwent neoadjuvant chemotherapy, interval debulking surgery, and adjuvant chemotherapy. She declined bevacizumab and PARPi maintenance therapy owing to the prohibitive expenses. The patient was administered off-label apatinib and achieved a progression-free survival of 54 months. Thus, apatinib may offer substantial therapeutic value as a first-line maintenance therapy in advanced ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: This is the first case report describing a patient with non-small cell lung cancer (NSCLC) harboring two rare human epidermal growth factor receptor 2 (HER2) exon 21 insertion mutations, who responded to furmonertinib treatment. Furmonertinib maybe one effective and economical treatment for NSCLC patients harboring HER2 mutations with minor side effects. Case description: We present a case report of a 49-year-old female diagnosed with stage IV lung adenocarcinoma who complained of irritating dry cough symptoms followed by chest tightness. Firstly, we describe the patient's treatment history, including failed third-line combination treatments of systemic chemotherapy with bevacizumab or carrelizumab or anlotinib, primary lung tumor recurrence, bilateral lung metastases progression, and new brain metastatic lesion detection. Next, we detail the patient's fourth-line treatment with radiotherapy for brain metastases and two cycles of bevacizumab plus Abraxane and cisplatin, however, the disease progressed and relapsed. After that, comprehensive genomic profiling revealed two HER2 exon 21 insertion mutations. Subsequently, the patient received targeted therapy with furmonertinib and achieved 11 months of progression-free survival. The patient received pyrrotinib therapy for 2 months after disease progression, but the disease continued to progress. In October 2023, the patient received therapy with furmonertinib again, and a month later, the disease went into partial remission. However, the patient died due to hypoproteinemia combined with severe pneumonia in December 2023. Conclusion: Furmonertinib may be effective for NSCLC patients with HER2 T8962A and L869R mutations and further studies are needed to confirm these results in prospective clinical trials. [ABSTRACT FROM AUTHOR]

Intravenous pembrolizumab 400 mg every 6 weeks was approved across tumor types based on pharmacokinetic modeling, which showed exposures consistent with previous standard dosing of 200 mg or 2 mg/kg every 3 weeks, and early results of cohort B of the phase 1 KEYNOTE-555 study. Results after ≥1 year of potential follow-up for all patients in cohort B of KEYNOTE-555 are presented. Patients aged ≥18 years with previously untreated stage III/IV melanoma received pembrolizumab 400 mg every 6 weeks for ≤18 cycles. The primary endpoint was objective response rate per RECIST v1.1 by blinded independent central review. Secondary endpoints included duration of response, progression-free survival, pharmacokinetics, and safety. Overall, 101 patients received pembrolizumab. Median projected follow-up was 21.9 months (range, 17.0–25.7). The objective response rate was 50.5% (95% CI: 40.4–60.6; 19 complete responses, 32 partial responses). Median duration of response was not reached (NR; range, 2.4+ to 21.0+ months). Median progression-free survival was 13.8 months (95% CI: 4.1–NR). Observed pharmacokinetic exposures were consistent with model predictions for pembrolizumab 400 mg every 6 weeks and other approved and tested schedules (2 mg/kg or 200 mg every 3 weeks). Grade 3–4 treatment-related adverse events occurred in 13 patients (12.9%). No deaths were considered treatment related. These results support the pharmacokinetic modeling and demonstrate that the benefit-risk profile of pembrolizumab 400 mg Q6W is consistent with that of 200 mg or 2 mg/kg every 3 weeks. Clinically meaningful objective response rate and durable progression-free survival within the expected range for first-line pembrolizumab were observed. Clinical trial registry: ClinicalTrials.gov, NCT03665597. [ABSTRACT FROM AUTHOR]

To investigate the prognostic factors of recurrent meningioma patients who underwent reoperation, so as to make relevant recommendations for the treatment. A retrospective analysis was performed on 73 patients with recurrent meningioma. Patients' clinical data were obtained from their medical records. Progression-free Survival (PFS) was defined as the interval from the date of surgery to the date of tumor recurrence, or to the date of the last imaging review. Overall survival (OS) was defined as the time from the date of surgery to death from any cause, or to the date of the last follow-up. The multivariate COX regression showed that dural attachment length (HR = 1.238, 95%CI1.011–1.516, P = 0.039) and WHO grade (HR = 2.184, 95%CI1.135–4.203, P = 0.019) were independent risk factors for tumor progression. The factors associated with survival in multivariate regression analysis were preoperative Karnofsky Performance Scale (KPS) (HR = 0.951, 95%CI0.923–0.979, P = 0.001), dural attachment length (HR = 1.520, 95%CI1.124–2.057, P = 0.007) and WHO grade (HR = 4.829, 95%CI1.891–12.331, P = 0.001). The dural attachment length (OR = 1.843, 95%CI1.236–2.748, P = 0.003) was the only risk factor associated with postoperative pulmonary infection. No correlation was observed between Simpson's grade and either PFS or OS. The dural attachment length is closely related to the prognosis of recurrent meningioma, which should be given importance during the perioperative assessment. [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]

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: Androgen receptor signaling inhibitors (ARSis), when administered sequentially or in combination with docetaxel and androgen deprivation therapy (ADT), have been shown to enhance overall survival (OS) and progression-free survival (PFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Nonetheless, the optimal sequence for administering chemotherapy and ARSis remains to be determined. Objective: To compare the efficacy of ARSis sequential therapy with ARSis combined therapy for mHSPC, and to evaluate the efficacy and safety of different combination regimens. Methods: The PubMed, Embase, Cochrane Central, and ClinicalTrials.gov databases were searched from their inception through 14 July 2024, to identify eligible phase III randomized clinical trials (RCTs) evaluating the combination or sequential use of docetaxel + ADT with abiraterone, enzalutamide, apalutamide, or darolutamide. The outcomes of interest included OS, PFS, time to prostate-specific antigen (PSA) progression, grade 3–5 adverse events (AEs), and serious adverse events (SAEs). Results: Five RCTs involving 2836 patients were included in the analysis. When comparing ARSis sequential therapy to ARSis combined therapy, no significant differences were observed in OS (Hazard Ratio (HR): 1.17, 95% Confidence Interval (CI): 0.69–1.96), PFS (HR: 1.03, 95% CI: 0.47–2.22), or time to PSA progression (HR: 0.48, 95% CI: 0.03–7.69). Within the different ARSis combined regimens, the triple therapies involving enzalutamide, abiraterone, and darolutamide demonstrated comparable efficacy and safety profiles in the overall population, and their efficacy in patients with high-volume disease or low-volume disease was also similar. Conclusion: ARSis sequential therapy did not significantly differ from ARSis combined therapy in improving OS and PFS among patients with mHSPC, and thus can be considered as a viable treatment option. [ABSTRACT FROM AUTHOR]

Background: Combining Trastuzumab with chemotherapy for HER2-positive gastric cancer shows treatment promise but may raise costs. We aimed to evaluate the cost-effectiveness of combining Trastuzumab with chemotherapy for HER2-positive gastric cancer treatment in Iran. Methods: We employed a partitioned survival model (PSM) to evaluate the cost-effectiveness of trastuzumab plus chemotherapy versus chemotherapy alone. The PSM framework included three distinct health states: progression-free, post-progression, and death. Clinical data, including overall survival and progression-free survival rates, were derived from the ToGA trial, a randomized controlled study. A bottom-up approach was used to calculate costs by considering drug costs, adverse event management costs and other disease management costs separately for the progression-free and post-progression states. The analysis was conducted from the Iranian healthcare system's perspective, considering direct medical costs. We performed a cost-effectiveness analysis to determine the optimal strategy by comparing the incremental cost-effectiveness ratio (ICER) to Iran's cost-effectiveness threshold, set at one to three times the GDP per capita. Additionally, we conducted sensitivity analyses to assess the robustness of our findings. Results: Both FOLFOX-based regimens were strongly dominated. In comparison, the CAPOX regimen cost $2,811.11 for 0.75 QALYs. Adding Trastuzumab to CAPOX increased the cost to $6,128 and improved effectiveness to 0.92 QALYs, resulting in an ICER of $19,089.94 per QALY, which is between 2 and 3 times the GDP per capita in 2022. Conclusion: The addition of trastuzumab to chemotherapy regimens improved clinical outcomes in HER2-positive gastric cancer patients. From an economic perspective, the CAPOX regimen is the most cost-effective option when considering a cost-effectiveness threshold of up to two times Iran's GDP per capita. However, when the threshold increases to three times the GDP per capita, the CAPOX + Trastuzumab regimen becomes the preferred choice. These findings provide valuable insights for healthcare policymakers in Iran. [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]

Purpose: The purpose of this study was to investigate the effects of postoperative complications on long-term survival after laparoscopic surgery for resectable colorectal cancer. Methods: We retrospectively included 204 patients who underwent laparoscopic surgery for colorectal cancer from January 2016 to June 2020. Results: Overall, 68 (33.3%) patients had postoperative complications, twelve (17.6%) of which were classified as Clavien–Dindo class 3a or higher. The 5-year overall survival rate of the non-complication and complication groups were 93.0% and 81.7%, respectively (p = 0.048; Kaplan–Meier analysis and log-rank test), and those among patients with stage III disease were 87.0% and 61.3%, respectively (p = 0.045). The 5-year disease-free survival rates were 85.6% and 77.4%, respectively (p = 0.042). Multivariable Cox proportional-hazards analysis revealed that nodal stage (hazard ratio, 8.392; 95% confidence interval, 1.892–37.175; p = 0.005) was an independent prognostic factor for overall survival, and postoperative complications (hazard ratio, 2.996; 95% confidence interval, 1.076–8.340; p = 0.036) were independent prognostic factors for disease-free survival. Conclusion: Postoperative complications were associated with poor oncological outcomes, especially among patients with stage III colorectal cancer, and independent prognostic factors for disease-free survival. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a malignancy with poor prognosis and high heterogeneity. For HER2-positive, PD-L1 negative metastatic GC patients, chemotherapy plus trastuzumab is the first-line therapy. However, such patients soon acquired resistance to treatment, especially to trastuzumab during the treatment. Improving the therapeutic resistance of HER2-positive, PD-L1 negative metastatic GC is still a dilemma. We present the case of a metastatic GC patient with HER2-positive and PD-L1-negative expression who suffered progression after a short remission with trastuzumab plus chemotherapy. The patient exhibited strong heterogeneity in the primary and metastatic lesions. His resistance to trastuzumab was overcome after the addition of a PD-1 inhibitor, after which he received a durable response for more than 8 months. In HER2-positive, PD-L1-negative metastatic GC, the addition of PD-1 inhibitors after first-line chemotherapy and trastuzumab treatment resistance may be an option. [ABSTRACT FROM AUTHOR]

Objective: Recent evidence suggests that elevated levels of PD-L1 expression may be linked to early resistance to TKI and reduced survival in NSCLC with EGFR mutations. This study aimed to characterize the clinical and molecular features of EGFR-mutated lung adenocarcinomas and determine the prognostic significance associated with high PD-L1 expression. Materials and methods: We conducted a retrospective chart review of 103 consecutive patients with advanced EGFR-mutated NSCLC, who received treatment between 01/01/2016 and 30/12/2020, at our institution. Results: Among the tumors, 17% (n = 18) exhibited high PD-L1 expression (≥50% tumor proportion score), which was associated with a lower prevalence of common EGFR mutations (56% vs. 82%, p = 0.03) and a higher frequency of complex EGFR mutations (28% vs. 7%, p = 0.02). Univariate analysis did not reveal any significant differences in first-line response, progression-free survival, or overall survival between the PD-L1 ≥50% and <50% groups. However, multivariate analysis demonstrated that PD-L1 ≥50% was independently associated with shorter survival (HR = 2.57; 95%CI[1.20–5.55]; p = 0.02), along with male gender (HR = 2.77; 95%CI[1.54–4.19]; p<0.005), presence of liver metastases (HR = 5.80; 95%CI[2.86–11.75]; p<0.005) or brain metastases (HR = 1.99; 95%CI[1.13–3.52]; p = 0.02), and poor general condition at diagnosis (ECOG 3 and 4) (HR = 10.69; 95% CI[4.42–25.85]; p<0.005). Additionally, a trend towards a higher frequency of de novo resistance was observed in the PD-L1 >50% group (7% vs. 17%, p = 0.19). Conclusion: High PD-L1 expression was more commonly found in lung adenocarcinomas with uncommon and complex EGFR mutations. Furthermore, high PD-L1 expression independently predicted poor survival. These findings warrant validation through prospective studies. [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]

Patients with advanced and recurrent cervical cancer often lack satisfactory treatment outcomes. Thus, it is necessary to seek reliable biomarkers that provide the ability to identify the disease at an early stage and predict the patient prognosis, providing new strategies for the treatment of cervical cancer. The sequencing data of ITGA3 were retrieved from public datasets. Immune infiltration and sensitivity of potential immunotherapy and chemotherapy have been analyzed between two subgroups. Functional analysis was applied to excavate the related pathways of ITGA3 in cervical cancer. Furthermore, the impact of ITGA3 in tumor progression has been verified in vitro. The results revealed that the level of ITGA3 was upregulated in cervical cancer, and was positively correlated with worse prognosis. The tumor microenvironment of patients in the high-risk group was immunosuppressed. Patients in high-risk group may not benefit from immunotherapy, but be may be sensitive to several chemotherapy drugs. Notably, the angiogenesis, epithelial mesenchymal transition, and PI3K pathway were increased in high-risk group. Collectively, ITGA3 is a marker of poor prognosis and promotes tumor progression by regulating PI3K/AKT pathway in cervical cancer. Our results provide new insights for potential molecular targeted therapy and prognostic prediction of cervical cancer. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, yet it carries significant risks, including acute kidney injury (AKI). In this study, we investigated the risk factors and clinical impact of AKI in patients undergoing CAR-T cell therapy. This retrospective study involved hematologic patients treated with CAR-T therapy. Clinical and laboratory data were collected, and clinical outcomes were monitored during follow-up after CAR-T infusion. AKI was defined according to KDIGO criteria. The outcome measures included early mortality, overall survival (OS), and disease-free survival (DFS). Among the 48 patients analyzed, 14 (29%) developed AKI, with a mean onset of 6 days after CAR-T infusion. The risk of AKI was associated with baseline performance status (OR 8.65, IC95% 6.2–12, p = 0.032) and the development of severe cytokine release syndrome post-therapy (OR 16.4 95%CI 1.9-138.5, p = 0.01). Patients with AKI more frequently required intensive care. Furthermore, severe AKI was independently associated with worse clinical outcomes, including reduced OS and DFS (HR 18.2, 95%CI 2.6–27.3, p = 0.003). Additionally, patients who developed AKI post-CAR-T therapy were more likely to progress to chronic kidney disease during follow-up. In conclusion, frail patients undergoing CAR-T therapy are at an increased risk of developing AKI, which can significantly affect both short- and long-term outcomes. Preventive strategies and early recognition of AKI are essential in these patients. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) for survival outcomes in bladder cancer patients treated with radical cystectomy. Methods: Studies assessing NLR's prognostic significance for bladder cancer after radical cystectomy were identified from PubMed, Embase, Web of Science, and Cochrane databases until April 2024. Survival outcomes analyzed included overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), cancer-specific survival (CSS), and progression-free survival (PFS). Results: The meta-analysis comprised 15 cohort studies with 8,448 patients. Multivariate analysis showed significantly shorter OS, CSS, DFS, and RFS in the high NLR group compared to the low NLR group. However, no significant difference in PFS was observed between the groups. Conclusions: NLR serves as an independent prognostic indicator for bladder cancer patients undergoing radical cystectomy, with elevated NLR associated with poorer survival. Further large-scale, prospective studies are warranted to validate the relationship between NLR and prognosis in bladder cancer. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42024549573. [ABSTRACT FROM AUTHOR]

Objective: This study explores the benefits of targeted-immunotherapy combination in third-line or beyond treatment for microsatellite stable (MSS) metastatic colorectal cancer (mCRC) in a real-world setting. Methods: Patients with MSS mCRC who were treated with either a targeted-immunotherapy combination or targeted therapy alone in the third-line or beyond setting at our hospital from August 2018 to August 2022 were included in the study. Inclusion criteria comprised patients treated with targeted therapy alone or in combination with immunotherapy. Effectiveness was compared between treatments, and patients with the potential to benefit from targeted-immunotherapy combination were identified. Results: Among 71 patients, 31 received targeted therapies alone (TT group) and 40 received a combination of targeted therapy and immunotherapy (TI group). The TI group had higher objective response rates (20% vs 3.2%) and disease control rates (82.5% vs 58.1%). The median progression-free survival was significantly better in the TI group (4.6 vs 4.1 months, P = 0.027). Liver metastasis was associated with poor prognosis, while patients with only lung metastases had the longest median progression-free survival of 12.3 months with combination therapy. Conclusion: The study indicates that targeted-immunotherapy combination offers more benefits than targeted therapy alone for MSS mCRC in the third-line or beyond setting. [ABSTRACT FROM AUTHOR]

High-dose melphalan at 200 mg/m2 (MEL-200) is the standard conditioning regimen before autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). Busulfan (BU) and cyclophosphamide (CY) can be used as alternatives when MEL is unavailable. However, most studies on BU/CY conditioning regimens were conducted before proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs) were available. This non-interventional comparative cohort study compared progression-free survival (PFS) between the MEL-200 and BU/CY in patients with MM treated with PIs and/or IMIDs. A total of 137 patients were analyzed (MEL-200,113 patients; BU/CY, 24 patients). The BU/CY group had a higher rate of PI and/or IMID use and very good partial response (VGPR) or complete remission (CR) at ASCT and post-ASCT maintenance. Median PFS was 29.7 and 46.8 months in the MEL-200 and BU/CY groups, respectively. In the multivariate analysis, PFS was significantly better in the BU/CY group. International Staging System Stage I and VGPR or CR at ASCT were significantly associated with longer PFS. No treatment-related mortality was observed in either group by day 100. The BU/CY conditioning regimen may be a viable alternative to the MEL-200 regimen in patients with MM who undergo ASCT after treatment with PIs and/or IMIDs. [ABSTRACT FROM AUTHOR]

Introduction: Chemoradiotherapy in head and neck cancer patients has a curative intent but often deteriorates nutritional status leading to sarcopenia and cachexia. Methods: In this observational and single-centered study, a prospective evaluation of several biochemical and anthropometrical parameters, weight loss, handgrip strength, visual analogue scale of appetite, questionnaires associated with malnutrition & quality of life and body composition (obtained by Bioelectrical Impedance Vector Analysis) was performed before and after high-dose cisplatin chemotherapy combined with radiotherapy in 60 patients affected by head and neck cancer. Oral nutritional supplements were used to reach the correct number of daily calories and proteins. Results and discussion: All patients completed radiotherapy as planned and the 96,4% of them did not interrupt chemotherapy for toxicity, reaching a total dose of at least 200mg/m2. Despite a rapid deterioration of body composition during treatment, nutritional support helped patients to maintain (or in some cases improve) anthropometric parameters from the end of chemoradiotherapy to the following 3 months. Low prealbumin and albumin pre-treatment led to higher risk of toxicities with consequent reduction of cisplatin dose intensity, whereas weight at the end of the treatment seems to be an interesting predicting factor for disease free and overall survival (p=0.007; p=0.015). [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) is associated with a high risk of endometrial cancer (EC). However, its impact on EC progression remains unclear. This meta-analysis examined the association between MetS and survival outcomes in EC patients. Methods: A comprehensive search of PubMed, EMBASE, and Web of Science databases up to May 22, 2024, was conducted. Two independent reviewers performed study selection, data extraction, and quality assessment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random effects model. Results: Nine studies comprising 13,579 endometrial cancer (EC) patients were included. Among these, 2,896 patients (21.3%) had MetS at the time of enrollment. The follow-up durations ranged from 3.4 to 14.2 years. The results showed that EC patients with MetS at baseline demonstrated significantly poorer overall survival (HR = 1.57, 95% CI = 1.19-2.07, p = 0.002; I² = 25%) and progression-free survival (HR = 1.33, 95% CI = 1.08-1.63, p = 0.007; I² = 16%). A similar association was observed for cancer-specific survival (HR = 1.26, 95% CI = 1.10-1.44, p = 0.001; I² = 0%). Subgroup analyses based on study characteristics showed consistent results across studies conducted in countries with different follow-up durations. Conclusion: This meta-analysis suggests that MetS is associated with poor survival outcomes in EC patients. Further prospective studies are required to validate our findings. Systematic review registration: PROSPERO, identifier CRD42024561654. [ABSTRACT FROM AUTHOR]

We propose a novel framework that addresses the deficiencies of Randomized clinical trial data subgroup analysis while it transforms ObservAtional Data to be used as if they were randomized, thus paving the road for precision medicine. Our approach counters the effects of unobserved confounding in observational data through a two-step process that adjusts predicted outcomes under treatment. These adjusted predictions train decision trees, optimizing treatment assignments for patient subgroups based on their characteristics, enabling intuitive treatment recommendations. Implementing this framework on gastrointestinal stromal tumors (GIST) data, including genetic sub-cohorts, showed that our tree recommendations outperformed current guidelines in an external cohort. Furthermore, we extended the application of this framework to RCT data from patients with extremity sarcomas. Despite initial trial indications of universal treatment necessity, our framework identified a subset of patients who may not require treatment. Once again, we successfully validated our recommendations in an external cohort. [ABSTRACT FROM AUTHOR]

Lung enteric-type adenocarcinoma (ETAC) is a rare subtype of non-small cell lung cancer (NSCLC), comprising approximately 0.6% of all primary lung adenocarcinomas. It is characterized by a tendency for early metastasis and a prognosis comparable to that of common lung adenocarcinoma. This case report described a patient with lung-ETAC who developed gastric metastasis. The patient underwent treatment with chemotherapy and a PD-1 inhibitor, resulting in disease remission with a progression-free survival (PFS) of 8 months. The follow-up time was 13 months. This case report was aimed to enhance understanding of the biological behavior of this rare tumor and provide insights into potential future treatment strategies. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to compare the safety and efficacy of drug-eluting bead (DEB) transarterial chemoembolization combined with lenvatinib and camrelizumab (DEB-TACE-Len-C) and DEB-TACE-Len for the treatment of unresectable hepatocellular carcinoma (uHCC). Methods: This retrospective study consecutively included uHCC patients who underwent DEB-TACE-Len-C or DEB-TACE-Len treatment at our hospital and Qujing Second People's Hospital from April 2020 to April 2022. In total, 85 patients were enrolled. There were 42 patients in the DEB-TACE-Len-C group and 43 patients in the DEB-TACE-Len group. The disease control rate (DCR), objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared between the two groups, and the factors influencing OS and PFS were analysed. Results: The ORR, DCR, PFS and OS were significantly greater in the DEB-TACE-Len-C group than in the DEB-TACE-Len group (ORR: 76.2% vs. 46.5%, P = 0.005; DCR: 88.1% vs. 67.8%, P = 0.039; PFS: 10 months vs. 6 months, P < 0.0001; OS: 24 months vs. 16 months, P = 0.0038). Multivariate Cox proportional hazard regression analysis revealed that portal tumour thrombus (PVTT) and therapeutic approach were independent factors affecting PFS and OS. There were no statistically significant differences in the incidence of AEs between the two groups (P > 0.05). Conclusion: Compared with DEB-TACE-Len, DEB-TACE-Len-C is an effective treatment option that can improve the tumour therapeutic response and prolong the OS and PFS in uHCC patients. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the interfractional volume changes of large (≥ 10 cm3) brain metastases (BMs) during fractionated gamma knife radiosurgery (FGKRS) to assess its predictive value for tumor control outcomes. Methods: The patients who underwent FGKRS for large BMs between January 2017 and December 2022 in our center were reviewed. The interfractional volume change was defined as the disparity in tumor volume (TV) measured between the magnetic resonance images acquired on the first treatment day and those obtained after 2 or 3 fractions during the course of FGKRS. Results: A total of 73 lesions in 70 patients with various primary pathologies were included. Over a median follow-up period of 11 months (range 1–77), the tumor control rate was 63%. Initial TV (cm3) was associated with progression free survival (PFS) and overall survival (OS) in both univariate and multivariate analyses (p = 0.01). Interfractional TV changes revealed an increase in 13 (17.8%) lesions, no change in 14 (19.2%) lesions, and a decrease in 46 (63.0%) lesions, with a mean volume reduction of 5% ± 0.12. Three cut-offs (5%, 10% and 15% volume decrement) were established and patients were divided into two groups based on each reference point. However, there were no significant differences in PFS and OS between the two groups, irrespective of the chosen cut-off value used. Conclusion: Interfractional volume changes of large BMs were not found to be associated with tumor control outcomes. Neither significant interfractional volume reduction nor significant volume increase necessarily predicts the tumor control, making early close monitoring essential after FGKRS. [ABSTRACT FROM AUTHOR]

Introduction: Desmoid tumors (DT) are rare, locally invasive tumors originating from connective tissue. Surgical intervention is no longer the standard treatment for DT, as systemic therapy gradually replaces it due to its superior efficacy. Despite the availability of various treatment modalities, there is a need for a first-line systemic treatment regimen that offers both effective disease control and acceptable safety profiles. Methods: To assess the efficacy and safety of different systemic treatment agents for DT, we conducted a systematic review and network meta-analysis. Eligible studies were identified through searches of PubMed, Embase, and the Cochrane Library databases, and data were extracted according to predefined inclusion criteria. Results: Three articles and clinical data from 295 patients with progressive and refractory DT were included in this Bayesian network meta-analysis. When considered by objective response rate (ORR), the efficacy of γ-secretase inhibitor versus placebo (OR 0.12, 95%CI 0.01–1.68) is superior to that of TKI (OR 0.49, 95%CI 0.03–7.62) and chemotherapy (OR 0.90, 95%CI 0.02–40.00). Vascular endothelial growth factor (VEGF)-TKI (OR, 0.09; 95% CI, 0.01–1.79) seemed to have the highest improvement in terms of 1-yr PFS rate, while chemotherapy seemed to have the highest improvement across all therapies in terms of 2-yr PFS rate across all therapies (OR, 0.06; 95 percent CI, 0.01–2.98). In terms of safety, the incidence of AEs is highest for γ-secretase inhibitor versus placebo (OR 0.16, 95%CI 0.02–1.55), while TKI is associated with the least AEs (OR 0.62, 95%CI 0.06–6.97). Conclusion: γ-secretase inhibitor provides superior local control of tumors, while chemotherapy and TKI may offer better long-term survival benefits. Among the three regimens, TKI demonstrated better treatment-related safety. These findings have important implications for guiding clinical practice in systemic treatment of DT. Highlights: The study conducted a systematic review and Bayesian network meta-analysis to evaluate the efficacy and safety of systemic treatment options for progressive and refractory desmoid tumors. The analysis included 3 RCT studies, and the primary clinical endpoints were progression-free survival and objective response rate. The network meta-analysis showed that γ-secretase inhibitors have better tumor response and more severe toxicity, while chemotherapy and TKI may have better long-term survival benefits. [ABSTRACT FROM AUTHOR]

The prognostic value of prostate-specific antigen (PSA) kinetics in primary high-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with novel hormonal therapy agents is still unclear. Here, we retrospectively reviewed the data of 102 patients with primary high-volume mHSPC who received novel hormonal therapy agents. The median follow-up was 32.25 ± 14.51 months and the median nadir PSA (nPSA) was 0.20 (0.06, 11.71) ng/mL after treatment. The mean time to nPSA was 10.82 ± 7.27 months and 55 patients (53.9%) had a PSA-density (PSA-D) ≤ 0.08 at 3-months. Univariate and multivariate Cox regression analyses showed that the absence of visceral metastases, nPSA ≤ 0.2 and PSA-D ≤ 0.08 were independent prognostic factors for better PFS and OS (all P < 0.05). Moreover, patients with nPSA ≤ 0.2 and PSA-D ≤ 0.08 had the best PFS and OS, and the combination of the nPSA and PSA-D had a better predictive accuracy for PFS and OS than nPSA and PSA-D alone. Thus, Visceral metastases, nPSA and PSA-D were independent prognostic factors for primary high-volume mHSPC patients treated with novel hormonal therapy agents. Patients with lower nPSA and PSA-D had a best survival outcome, and the combination of nPSA and PSA-D had a better effect on prognosis predicting. [ABSTRACT FROM AUTHOR]

Recurrent high-grade intracranial malignancies have a grim prognosis and uniform management guidelines are lacking. Re-irradiation is underused due to concerns about irreversible side effects. Pulsed-reduced dose rate radiotherapy (PRDR) aims to reduce toxicity while improving tumor control by exploiting dose-rate effects. We share our initial experience with temporally modulated pulsed proton re-irradiation (TMPPR), focusing on workflow, safety, feasibility, and outcomes for the first patient cohort. TMPPR was administered to patients with recurrent or progressive central nervous system malignancies using intensity modulated proton therapy with three fields. Patient and treatment data were collected, responses categorized using RANO assessment, and toxicities graded using CTCAE v5.0. Five patients received TMPPR between October 2022 and May 2023, with a median age of 54 years (Range: 32–72), and a median time from initial radiotherapy to re-RT of 23 months (Range 14–40). Treatment was completed without delay, with a median dose of 60 GyRBE in 30 fractions. Initial treatment response assessment showed complete (n = 1) or partial (n = 3) responses. Limited toxicity was observed, primarily grade 2 alopecia and one case of radiation necrosis graded at 2. This early experience demonstrates the feasibility of TMPPR delivery, highlighting the importance of prospective evaluations in the re-irradiation setting. [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]

This study was designed to investigate the demographics, treatment patterns, and clinical outcomes of patients newly diagnosed with high-grade serous ovarian cancer (HGSOC) in 3 medical centers in Taiwan before the integration of poly (ADP-ribose) polymerase inhibitors in clinical practice. A retrospective analysis was conducted on data from patients diagnosed with HGSOC between January 2014 and December 2018 and followed-up for a minimum of 12 months after diagnosis. Descriptive statistics were used to analyze the data, while survival rates were evaluated using the Kaplan‒Meier method. There were 251 patients included in the analysis, and 98.8% received platinum plus paclitaxel chemotherapy (PPCT). Primary cytoreductive surgery (PCS) and interval debulking surgery (IDS) were performed in 78.9% and 17.1% of patients, respectively. The percentage of optimal surgery was higher in the IDS cohort than in the PCS cohort (83.8% vs. 53.6%). Bevacizumab was used as initiation therapy in 16.7% of patients, and maintenance therapy was administered in 6.8%. Advanced age, IDS, and suboptimal surgery were independent poor prognostic factors associated with lower overall survival (OS). Patients with optimal surgery had significantly lower OS and progression-free survival in the IDS cohort than in the PCS cohort. The predictive accuracy was good for OS at the 1-year follow-up. Advanced age, IDS, and residual disease are associated with poor OS in patients with HGSOC. Compared to PCS, IDS provides a higher likelihood of optimal surgery but results in a lower probability of survival for patients with HGSOC in Taiwan. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize the clinicopathological features and prognostic factors of T1/2 size (<4 cm) gingival squamous cell carcinoma (SCC) and to verify the impact of bone invasion. This was a single-centre, retrospective cohort study involving 206 patients with gingival SCC (maxilla or mandible), treated between 2000 and 2020. The patients were divided into three subgroups based on tumour size and bone invasion. The 5-year overall survival (OS) and disease-free survival (DFS) were 80.6% and 67.6%, respectively. Histological differentiation, advanced T stage, positive resection margin, bone invasion, and postoperative adjuvant therapy were associated with a poor prognosis (P < 0.05). Multivariate Cox analysis indicated that only histological differentiation (hazard ratio (HR) 2.68, P = 0.007) and bone invasion (HR 2.08, P = 0.036) were significantly associated with DFS. Bone invasion was observed in 145 (70.4%) patients, of whom 43 (20.9%) had a T1/2 size tumour. The subgroup with bone invasion and T1/2 size showed significantly worse OS and DFS when compared to the subgroup without bone invasion and similar or worse survival when compared to the subgroup with bone invasion and T3/T4 size. Histological differentiation and bone invasion were poor prognostic factors for gingival SCC, even in cases with small-sized tumours. For suspected bone invasion in small-sized tumours, an adequate bone margin is necessary and postoperative adjunctive therapy needs to be considered. [ABSTRACT FROM AUTHOR]

Objective: Radical surgery is the mainstay treatment for adenocarcinoma of the esophagogastric junction. The presence of microscopic residual tumor tissue after curative-intent surgery is associated with recurrence. This study compared the outcomes of patients with microscopic residual tumor (Residual+ group) and those without microscopic residual tumor (Residual- group). Material and Methods: We retrospectively reviewed the medical records of 71 patients with adenocarcinomas of the esophagogastric junction who underwent curative-intent surgery between January 2005 and August 2018. We evaluated the clinical and pathological characteristics and compared recurrences, rates and patterns, between groups. Five-year overall survival (OS) and 3-year disease-free survival (DFS) were analyzed by Kaplan-Meier analysis. Results: Nineteen (26.8%) patients had microscopic residual tumors, consisting of 8 (11.3%) with positive resection margins, 10 (14.0%) with malignant cells from peritoneal washing fluid cytology, and 1 (1.4%) with both. The median OS in the Residual- group was significantly better than that in the Residual+ group (31.3 vs 11.9 months, P = 0.003). The Residual- group had better 5-year OS (26.2% vs 11.9%, P = 0.015) and 3-year DFS (24.4% vs 9.8%, P = 0.003) than the Residual+ group. During follow-up period, 48% of the patients in the Residual+ group experienced recurrent disease, with a median follow-up time at 7.7 months. Distant metastasis was the most common site of recurrence. Conclusion: Microscopic residual tumor after resection is associated with poorer survival outcomes and higher recurrence rates. Curative surgery should aim to achieve R0 resection in all patients with resectable adenocarcinomas of the esophagogastric junction. [ABSTRACT FROM AUTHOR]

Background: Concurrent chemoradiotherapy (CCRT) is used as the primary treatment modality for currently limited cervical cancer and lacks non-invasive quantitative parameters to assess clinical outcomes of treatment for cervical cancer treatment. Purpose: To develop nomograms based on clinical prognostic factors and apparent diffusion coefficient (ADC) in predicting downstaging and progression-free survival (PFS) after CCRT for cervical cancer. Material and Methods: X-tile was used to calculate the optimal threshold for ΔADCmean(%) for prognostic stratification. Kaplan–Meier curves were used to calculate the difference in PFS between high- and low-risk groups. Univariate and multivariate Cox proportional risk regression models were used to identify clinical and radiological risk factors for prognosis and construct a prognostic nomogram model. Results: ΔADCmean(%) was significantly correlated with tumor downstaging; the area under the receiver operating characteristic curve (AUC) was 0.868. X-tile showed that the optimal threshold for ΔADCmean(%) to diagnose prognosis was 40.8. Kaplan–Meier curves showed that the low-risk population in the training group had significantly longer PFS within 3 years (P < 0.001). Multivariate Cox regression showed that ΔADC (%) is independent risk factor for PFS. The C-index of ΔADC(%) predicting 3-year PFS in the training set is 0.761 and the C-index of the nomogram model is 0.862. Conclusion: ΔADCmean(%) is a non-invasive biomarker for predicting tumor downstaging in cervical cancer after CCRT. The nomograms based on ΔADCmean(%) predict PFS of patients with cervical cancer with moderate accuracy. [ABSTRACT FROM AUTHOR]

Introduction: Reactive oxygen species modulator 1 (Romo1) is a novel protein that is critically involved in the intracellular production of reactive oxygen species. Evidence has revealed that Romo1 is associated with treatment outcomes of various human malignancies, including lung cancer. However, the clinical implications of this protein in surgically resected lung cancers harboring epidermal growth factor receptor (EGFR) mutations have not been investigated. Methods: Data were collected from patients who underwent curative resection of EGFR-mutant lung adenocarcinoma. Romo1 protein expression levels were measured in the tumor tissue using immunohistochemical staining and evaluated semi-quantitatively using the histochemical score. Univariate and multivariate analyses were performed to identify the clinicopathological parameters that may be associated with clinical outcomes. Results: A total of 98 samples were analyzed. Using the cutoff H score of 200, the population was classified into low (n = 73) and high (n = 25) Romo1 groups. Romo1 expression was significantly higher in smokers, patients with stage III disease, and patients who experienced recurrence after surgery (all p < 0.05). Multivariate analyses showed that advanced-stage and poorly differentiated cancers were associated with shorter disease-free survival (DFS). In addition, high Romo1 expression was independently associated with poor DFS (hazard ratio = 2.18, 95% confidence interval: 1.10–4.32, p = 0.0261). Conclusions: Our data showed that Romo1 overexpression was significantly associated with early recurrence in patients with resected EGFR-mutant lung adenocarcinoma. Although large-scale studies are required, Romo1 may play a prognostic role in this patient population. [ABSTRACT FROM AUTHOR]

Background: There remains a lack of studies addressing the stromal background and fibrosis features and their prognostic value in liver cancer. qFibrosis can identify, quantify, and visualize the fibrosis features in biopsy samples. In this study, we aim to demonstrate the prognostic value of histological features by using qFibrosis analysis in liver cancer patients. Methods: Liver specimens from 201 patients with hepatocellular carcinoma (HCC) who underwent curative resection were imaged and assessed using qFibrosis system and generated a total of 33 and 156 collagen parameters from tumor part and non-tumor liver tissue, respectively. We used these collagen parameters on patients to build two combined indexes, RFS index and OS index, in order to differentiate patients with early recurrence and early death, respectively. The models were validated using the leave-one-out method. Results: Both combined indexes had significant prediction value for patients' outcome. The RFS index of 0.52 well differentiates patients with early recurrence (p < 0.001), and the OS index of 0.73 well differentiates patients with early death during follow-up (p = 0.02). Conclusions: Combined index calculated with qFibrosis from a digital readout of the fibrotic status of peri-tumor liver specimen in patients with HCC has prediction values for their disease and survival outcomes. These results demonstrated the potential to transform histopathological features into quantifiable data that could be used to correlate with clinical outcome. [ABSTRACT FROM AUTHOR]

Introduction: This study explored the failure pattern and clinical outcomes in patients with ependymoma undergoing radiotherapy. Methods: Between January 2004 and June 2022, we included 32 patients with ependymoma who underwent radiotherapy as part of the multimodality treatment at our institution. Of these, 27 (84.4%) underwent adjuvant radiotherapy, four received radiotherapy after local recurrence, and one received definitive CyberKnife radiotherapy (21 Gy in three fractions). The median prescribed dose was 54 Gy in patients who received conventional radiotherapy. We analyzed the local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and potential prognostic factors. Results: The median age was 29.8 years. Approximately 28.1% were pediatric patients. Fifteen tumors (46.9%) were World Health Organization (WHO) grade II, 10 (31.3%) were WHO grade III, and seven (22.8%) were WHO grade I. Among them, 15 patients (46.9%) had posterior fossa tumors, 10 (31.3%) had supratentorial tumors, and seven (22.8%) had spinal tumors. Of the 31 patients who underwent upfront surgical resection, 19 (61.3%) underwent gross total resection or near-total resection. Seventeen of 19 patients with first failures (89.5%) had isolated local recurrences. Of the 19 patients with disease progression, 11 (57.9%) were disease free or had stable disease after salvage therapy, and five (26.3%) had disease-related mortality. Most of the first local recurrences after radiotherapy occurred infield (13 of 16, 81.3%). The 5-year LPFS, DMFS, PFS, and OS rates were 48.5%, 89.6%, 45.1%, and 88.4%, respectively, at a median follow-up of 6.25 years. Subtotal resection was associated with poorer LPFS and PFS in patients with intracranial ependymoma (hazard ratio = 3.69, p = 0.018, for LPFS; hazard ratio = 3.20, p = 0.029, for PFS). Conclusion: Incorporating radiotherapy into multimodal treatment has led to favorable outcomes in patients with ependymoma, and the extent of resection is a prognostic factor for the local control of intracranial ependymoma. [ABSTRACT FROM AUTHOR]

Objective: Extragonadal germ cell tumours have a more unfavourable prognosis than gonadal germ cell tumours. We aimed to evaluate the survival analysis, response rates, and factors affecting responses to high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) in patients with relapsed/refractory extragonadal germ cell tumours. Methods: This study included patients diagnosed with extragonadal germ cell tumours who underwent HDCT + ASCT between November 2016 and January 2023 at Gülhane Training and Research Hospital. Clinical characteristics and follow-up data from patient records and the hospital's electronic system were retrospectively analysed. Patients under 18 years of age and those without medical records were excluded. Patient characteristics, post-HDCT progression-free survival (PFS), overall survival (OS) data, and factors affecting survival were examined. The relationship between clinical factors and OS/PFS was analysed. Results: Twenty-five patients were included in this study. Complete response (CR) was observed in seven patients (28%), partial response (PR) was observed in nine patients (36%), stable disease (SD) was observed in one patient, and progressive disease (PD) was observed in eight patients (32%) after HDCT + ASCT. The median follow-up period was 25.4 months. The median PFS and OS after HDCT + ASCT were calculated as 6.1 months and 12.2 months, respectively. Conclusions: Salvage HDCT + ASCT is an option in the treatment of extragonadal germ cell tumours, offering the potential for prolonged survival and curing. [ABSTRACT FROM AUTHOR]