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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]

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]

Magnetic resonance image-guided brachytherapy is essential in the management of locally advanced cervical cancer. This study compares disease and toxicity outcomes in cervical cancer patients treated with 24 Gy/3 fractions (Fr) versus the conventional 28 Gy/4 Fr. This retrospective study included 241 consecutive patients with International Federation of Gynecology and Obstetrics 2018 stage IB to IVA cervical cancer treated with definitive chemoradiation between April 2014 and March 2021. Disease-free survival (DFS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Cumulative incidence of local failure (LF), distant failure (DF), and G2+ gastrointestinal (GI), urinary and vaginal toxicity were estimated using the cumulative incidence function with death as a competing risk and compared using Gray's test. Of the 241 patients, 42% received 24 Gy/3 Fr and 58% received 28 Gy/4 Fr. With a median follow-up of 3.2 (range, 0.2-9.2) years, there were 14 local, 41 regional nodal, and 51 distant failures in 63 (26%) patients. No significant differences were found between the 24 Gy/3 Fr and 28 Gy/4 Fr groups in 3-year DFS (77% vs 68%, P =.21), the 3-year cumulative incidence of LF (5% vs 7%, P =.57), DF (22% vs 25%, P =.86), G2+ GI toxicity (11% vs 20%, P =.13), or G2+ vaginal toxicity (14% vs 17%, P =.48), respectively. The 3-year cumulative G2+ urinary toxicity rate was lower in the 24 Gy/3 Fr group (9% vs 23%, P =.03). Patients with cervical cancer treated with 24 Gy/3 Fr had similar DFS, LF, DF, GI, and vaginal toxicity rates and a trend toward a lower G2+ urinary toxicity rate compared with those treated with 28 Gy/4 Fr. A less resource-intensive brachytherapy fractionation schedule of 24 Gy/3 Fr is a safe alternative to 28 Gy/4 Fr for definitive treatment of cervical cancer. [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]

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]

Keratin 17 (K17) is frequently overexpressed, associated with poor prognosis in various cancers, and contributes to p27 degradation during cancer progression. Using immunohistochemistry, we evaluated K17 and p27 expression and assessed their biological behavior and prognostic significance in 326 colorectal cancers. High K17 expression was associated with poorly differentiated tumors, high pT classification, and lymph node metastases. Low p27 expression was associated with large tumors, high pT classification, lymphovascular invasion, and lymph node metastases. The overall survival of patients with high K17 expression was significantly worse than that of patients with low K17 expression [hazard ratio (HR) = 1.805, 95% confidence interval (CI) 1.169–2.787; p = 0.007]. Patients with low p27 expression showed significantly worse overall survival than those with high p27 expression (HR = 3.082, 95% CI 1.722–5.517; p < 0.001). When combining the results of K17 and p27 expression, the K17highp27low expression group showed the worst overall survival. On the contrary, the K17high/lowp27high group showed the best overall survival (p < 0.001). Therefore, K17highp27low expression is an independent poor prognostic factor in colorectal cancer. Thus, high K17 and low p27 expression correlate with aggressive clinicopathologic behavior and can be used as poor prognostic markers in colorectal cancer. [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: 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]

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]

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]

Background: The systemic immune-inflammation index (SII) is an effective tool for predicting the prognosis of patients with cancer. However, its value in patients with locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) undergoing definitive chemoradiotherapy has yet to be addressed. Therefore, we aimed to retrospectively investigate the prognostic significance of the pretreatment SII on the survival outcomes of patients with unresectable LA-PDAC treated with concurrent chemoradiotherapy (C-CRT). Methods: The study included 163 patients with LA-PDAC who had received C-CRT. Using receiver operating characteristic (ROC) curve analysis, the utility of a pre-C-CRT cutoff that could stratify survival results was investigated. The primary and secondary endpoints were the correlations between SII levels and overall survival (OS) and progression-free survival (PFS). Results: At a median follow-up period of 15 months (range: 3.2-94.5), the median OS and PFS rates for the entire group were 15.7 months (95% confidence interval [CI]: 13.4-17.9), and 7.8 months (95% CI: 6.1-9.4), respectively. We divided the patients into 2 SII cohorts based on the ROC curve analysis (area under the curve [AUC]: 71.9%; sensitivity: 68.9%; specificity: 66.7%): SII < 538 (N = 70) and SII ⩾ 538 (N = 93). Comparative survival analysis showed significantly inferior median OS (13.0 vs 25.4 months; P <.001) and PFS (7.0 vs 15.2 months; P =.003) in patients with SII ⩾ 538 compared with those with SII < 538 before treatment. In multivariate analyses, the Eastern Cooperative Oncology Group (ECOG) performance of 2, N1-2 lymph node, CA 19-9 > 90 U/mL, and SII ⩾ 538 status emerged as independent prognosticators of inferior OS and PFS. Conclusions: Present results indicate that patients with unresectable LA-PDAC who underwent C-CRT and had a pretreatment SII ⩾ 538 had significantly worse OS and PFS outcomes compared with those with lower SII values. [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]

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]

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]

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]

Abstract\nKEY MESSAGESCancer remains a major global cause of death, posing significant treatment challenges. The interactions between tumor cells and the tumor microenvironment (TME) are crucial in influencing tumor initiation, progression, metastasis, and treatment response. There has been significant research and clinical interest in targeting the TME as a therapeutic approach in cancer, with advancements being made through drug development. Histamine binds to HRH1 receptors on the TME, which inhibit CD8+ T cell activity, promote tumor growth, and contribute to resistance against immunotherapy. By inhibiting CD8+ T cells, the effectiveness of immunotherapies targeting these cells is reduced. By blocking the HRH1 pathway, H1-antihistamines can mitigate this suppression and enhance the response to immunotherapies that target CD8+ T cells. Therefore, understanding the role of histamine and its potential impact on T cells and the role of H1-antihistamines in improving immune-oncology (I/O) agents’ efficacy ultimately could lead to more effective cancer therapies. The objective of this review is to examine the current literature to investigate the potential role of H1-antihistamines on the effectiveness of I/O drugs and their role in enhancing treatment against cancer. We conducted a comprehensive literature search, which included multiple databases including PubMed, Google Scholar, and EMBASE, as well as a search of oncology congresses. Our literature review initially identified thirty studies. Twenty-three of these were excluded for failing to meet inclusion criteria, which varied from study design to the type of antihistamines and patient populations involved. The clinical studies investigated the effect of different generations of H1-antihistamines in combination with I/O treatments on patients’ outcomes. The findings from these studies indicated that patients using H1-antihistamines concomitantly with I/O agents experienced longer median overall survival (mOS), progression-free survival (mPFS), or improved survival compared to those who did not use antihistamines. Additionally, these trials differentiated between cationic and non-cationic H1-antihistamines, revealing that users of cationic antihistamines had overall better outcomes in terms of longer mOS and mPFS. The assessed trials were consistent in their comparisons of quantitative and qualitative, efficacy, and safety outcomes.Checkpoint inhibitors represent a significant breakthrough in cancer treatment; however, only 20-40% of patients respond to immunotherapies due to many factors, among them the highly immunosuppressive conditions of the TME in some cancer types. H1-antihistamines have been shown to potentiate the activity of immunotherapy by enhancing T cell activation in the TME. We reviewed the role of H1-antihistamines on clinical activity of immuno-oncology agents and integrated key clinical studies into a comprehensive resource for the first time, offering invaluable insights for future research. Drawing from our extensive experience in immuno-oncology clinical trials, the manuscript also provides practical recommendations for future research and therapeutic strategies to be implemented effectively. [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]

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]

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]

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]

Identifying clinical features that are associated with recurrence of endometrioid endometrial carcinoma (EEC) in patients with diabetes mellitus (DM). A single-center retrospective cohort study was performed on patients with a diagnosis of both DM and Stage I EEC. Clinical and pathologic features were analyzed in relation to 5-year progression free survival (PFS). Kaplan-Meier Curves and Cox proportional hazard ratios were utilized to assess effect on 5-year PFS. A total of 539 patients were included, with biopsy proven recurrence in 86 (18 %), and 456 (82 %) with no evidence of recurrence. Age, BMI, HgbA1c, metformin use, number of antihyperglycemic medications, use of adjuvant radiation, and surgical approach were not associated with differences in PFS. Presence of end-organ complications associated with diabetes was correlated with worse PFS (HR 1.78, 95 % CI 1.1–2.9, P = 0.02), and specifically diabetic neuropathy was associated with higher rates of recurrence (HR 3.6, 95 % CI 2.1–6.2, P < 0.01). In this cohort, PFS was independently associated with extent of myoinvasion (HR 2.33, 95 % CI 1.4–3.7, P < 0.01) as well as both microsatellite instability (HR 3.43, 95 % CI 1.8–6.6, P < 0.01), and no specific molecular profile (HR 0.3, 95 % CI 0.2–0.6, P < 0.01) molecular subtypes. In patients with DM and EEC, extent of myoinvasion and TCGA molecular subtype correlated with worse PFS. Control of DM as evidenced by HgbA1c, BMI, and use of antihyperglycemic medications did not correlate with PFS in our cohort of patients with Stage I EEC, while the presence of diabetic neuropathy was associated with a higher risk of recurrence. These results highlight importance of evaluating diabetes severity and molecular subtype in endometrial cancer patients. • Diabetic neuropathy is associated with higher rates of endometrioid endometrial carcinoma (EEC) recurrence. • Obesity, hemoglobin A1C, and use of antihyperglycemic medications is not associated with EEC recurrence rates. • Myoinvasion, microsatellite instability, and no specific molecular subtype is associated with increased EEC recurrence. [ABSTRACT FROM AUTHOR]

We assessed real-world trends in the use of maintenance therapy [MT] (i.e., polyADP-ribose polymerase inhibitors (PARPi) and/or bevacizumab following platinum-based chemotherapy), among U.S. patients with ovarian cancer. Using Medicare and commercial administrative health claims data from Optum's de-identified Clinformatics® Data Mart Database, we identified patients who had been diagnosed with ovarian cancer between January 1, 2010, and March 31, 2021, and received platinum-based chemotherapy and MT. Multivariable logistic regression and Cox proportional hazards regression were used to evaluate associations between demographic and clinical characteristics and MT use. Our study included 6339 patients, with a median age of 70 years. The majority were White (70.1 %), Medicare-insured (71.9 %), and were treated in the South (42.5 %). Of the 31.5 % who received MT, 18.1 % received bevacizumab alone, 10.2 % PARPi alone, and 3.3 % both. After adjusting for insurance type, PARPi and bevacizumab use increased significantly from 2017 to 2020. Patients with a high Elixhauser comorbidity index were more likely to receive MT than were patients with a low index [OR (95 % CI): 1.46 (1.28–1.67), p < 0.0001]. PARPi use was significantly associated with treatment in the South [1.42 (1.10–1.83), p = 0.01]. Compared to patients who received neither agents, those who received bevacizumab, alone or in combination with PARPi, had a higher risk of death [HR = 2.02 (95 % CI: 1.70–2.28, p < 0.0001) and 1.66 (1.24–2.23), p = 0.001, respectively]. The majority of patients with ovarian cancer are not utilizing maintenance therapy after platinum-based chemotherapy. Age, comorbidity status, and geographic region of treatment were associated with MT use. Understanding the factors and real-world outcomes associated with MT use is important to support patients in making value concordant and informed decisions. • Age, comorbidity status, and geographic region of treatment were associated with ovarian cancer maintenance therapy use. • After adjusting for insurance type, both PARPi and bevacizumab use increased significantly from 2017 to 2020. • We found relatively low use of PARPi plus bevacizumab, despite being associated with a longer progression-free survival. [ABSTRACT FROM AUTHOR]

To determine the impact of adjuvant therapy on oncologic outcomes in patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, or II endometrial clear cell carcinoma (ECCC). We conducted a retrospective review at 4 international institutions. Patients with newly diagnosed clinical stage I or II disease of either clear cell or mixed histology with a clear cell component treated between 01/01/2000–12/31/2015 were included. Oncologic outcomes were assessed for patients based on adjuvant treatment received, including chemotherapy, radiation, or chemotherapy with radiation. Of 125 patients identified and analyzed, 77 (61.6%) had clear cell histology and 118 (94.4%) had stage I disease. Median age at diagnosis was 65 years (range, 33–91). All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment. Twenty-five patients (20.0%) underwent surgical management alone and 100 (80.0%) received adjuvant therapy: 20 (16.0%) received postoperative chemotherapy, 47 (37.6%) received postoperative radiation, and 33 (26.4%) received postoperative chemotherapy with radiation. Median follow-up was 88.4 months (range, <1–234). Progression-free survival (PFS) or overall survival (OS) did not significantly differ between surgery alone and type of adjuvant therapy (P = 0.18 and P = 0.56, respectively). Patients with mixed ECCC did not have a survival advantage over those with pure ECCC (5-year PFS rate, 85.0% vs 82.7%, P = 0.77; 5-year OS rate, 88.3% vs 91.2%, P = 0.94). Receipt of adjuvant therapy in surgically staged I/II ECCC did not appear to offer a survival advantage over observation alone. Adjuvant therapy in early-stage ECCC with consideration of molecular classification should be evaluated. • Radiation only was the most common (38%) adjuvant therapy in patients with stage I-II endometrial clear cell carcinoma (ECCC) • Positive cytology impacted risk of recurrence and age > 65 years impacted overall survival in this cohort of patients • Survival outcomes of surgically staged patients with stage I-II ECCC were not impacted by receipt of adjuvant treatment • Patients with tumors of "pure" clear cell vs "mixed" clear cell histology had no difference in survival [ABSTRACT FROM AUTHOR]

To evaluate the significance of response assessment with magnetic resonance imaging (MRI) during chemoradiotherapy (CRT) for outcomes of adenocarcinoma of the cervix. A retrospective analysis of 102 patients diagnosed with FIGO 1B3-IVa cervical adenocarcinoma was conducted. Patients underwent definitive CRT and brachytherapy. Mid-treatment MRI-assessments were used to evaluate tumor response during radiotherapy, focusing on tumor volume reduction rate (TVRR), which was defined as an optimal reduction rate from initial tumor volume for tumor progression. Locoregional recurrence (LRR), distant metastasis (DM), progression-free survival (PFS) and overall survival (OS) rates according to the tumor response were analyzed. Forty-five (44.1 %) of 102 patients experienced tumor downstaging during CRT, with 72 (70.5 %) demonstrating a complete response on post-treatment MRI three months after radiotherapy. With a median follow-up of 35.5 months, the 3-year PFS and overall OS rates for all patients were 60.0 % and 84.0 %, respectively. LRR and DM rates at 3 years were 25.2 % and 23.3 %, respectively. Patients with TVRR≥81.8 % had significantly longer 3-year PFS (75.4 % vs. 36.2 %, P < 0.001) and OS (93.2 % vs. 69.0 %, P = 0.002) rates than the other patients with TVRR<81.8 %. LRR (10.6 % vs. 45.6 %, P = 0.003) and DM (14.6 % vs. 33.5 %, P = 0.008) rates at 3 years were significantly lower in TVRR≥81.8 % group compared to TVRR<81.8 % group. In the multivariate analysis, positive initial lymph node (hazard ratio [HR], 2.11; confidence interval [CI], 1.25–3.87; P = 0.02] and TVRR (HR, 0.42; CI, 0.19–0.93; P = 0.03) were significantly associated with PFS. Mid-treatment MRI assessment is crucial and higher rates of tumor volume reduction during radiotherapy indicates better prognosis for tumor recurrence and patient survival in cervical adenocarcinoma. [Display omitted] • We conducted a multicenter retrospective study on the significance of mid-treatment MRI in cervical adenocarcinoma. • The optimal tumor volume reduction rate using mid-treatment MRI for tumor progression was 81.8 %. • Higher tumor volume reduction rate patients had significantly longer 3-year PFS (75.4 % vs. 36.2 %, P < 0.001) than non-downstaged patients. • Positive lymph node and tumor downstaging were significant factors for PFS in the multivariate analysis (P = 0.02). [ABSTRACT FROM AUTHOR]

In patients with platinum-sensitive relapsed ovarian cancer (PSROC) harboring pathogenic/likely pathogenic variants (PV) in BRCA1 and BRCA2 genes, olaparib maintenance monotherapy (OMT) is a viable option. Our study aimed to evaluate the impact of different BRCA1/2 PV in survival outcomes and safety of OMT in BRCA1/2 -mutated PSROC patients, focusing on the type and location of PV. We assessed the outcomes of 100 BRCA1/2 -mutated PSROC patients treated at our institute, analyzing progression-free survival (PFS) and overall survival (OS). Germline and tumor BRCA1/2 genotyping was conducted using Illumina's next-generation sequencing (NGS). PFS and OS were significantly shorter in PSROC patients with PV in BRCA1 compared to those with PV in BRCA2 (PFS:14.0 vs. 38.8 months, p = 0.007, OS: 21.8 vs. 62.0 months, p = 0.011). Notably, there was a significant difference in PFS based on the intragenic location of BRCA1 PV, with shorter PFS in patients with 1st/2nd relapse, harboring PV in BRCA1 RING domain compared to those with PV in the DNA binding domain (DBD) and BRCT domains (12.4 vs. 23.0 months, p = 0.046). No differences in PFS and OS were observed between patients with germline versus somatic BRCA1/2 PV (PFS:14.9 vs.19.3, p = 0.316, OS: not reached vs. 25.8 months; p = 0.224). However, there were significant differences in the reasons for OMT discontinuation between patients with germline and somatic BRCA1/2 PV, primarily due to adverse side effects. In summary, the type and location of BRCA1 and BRCA2 PV provide additional insight into the expected survival outcomes of olaparib MT in PSROC patients. Trial registration number: ISRCTN42408038, Name of registry: ISRCTN registry, Date of registration: 24/11/2015. • BRCA1/2 mutation location impacts the outcome of relapsed ovarian cancer patients on olaparib maintenance monotherapy (OMT). • Patients on OMT with BRCA1 pathogenic variant (PV) had shorter progression free survival (PFS) compared to BRCA2 PV. • Patients on OMT with PV in BRCA2 or in BRCA1 DNA binding domain had better PFS compared to PV in BRCA1 RING domain. • No significant difference in PFS between patients on OMT with germline or somatic BRCA1/2 PV was observed. • Adverse events in patients on OMT were not significantly different between germline and somatic PV in BRCA1/2. [ABSTRACT FROM AUTHOR]

This study was conducted to determine the optimal monitoring after initial treatment of ovarian clear cell carcinoma (OCCC) using data from patients enrolled in the Japanese Gynecologic Oncology Group (JGOG) 3017 study. The JGOG study evaluated the efficacy of an irinotecan and cisplatin combination regimen compared with that of a paclitaxel and carboplatin regimen for OCCC patients who underwent primary surgery. Yielding 619 total patients in this study, to analyze progression-free and overall survival, the hazards over time were estimated using kernel smoothing curves to identify the peak of event occurrence. The number of progression events was summed by progression site, and the cumulative incidence proportion was estimated for the major progression sites, considering competing risks. The peak hazard for progression or death was observed at 12 months post-treatment, and most events were observed by 24 months. The hazard for death peaked at 18 months post-treatment, with most events being observed by 48 months. The hazard for lung, liver, and spleen metastases remained constant for 18 months post-treatment, with a decreasing trend thereafter; most events were observed by 18 months. The hazard for peritoneal dissemination was constant for 12 months, with a decreasing trend thereafter, with most exacerbations observed by 24 months. The risk of pelvic recurrence peaked at 6 months, with most exacerbations observed by 24 months. The incidence of progression events for OCCC peaked at 12 months and most progression events occurred within 24 months. Close follow-up for the initial 24 months post-treatment and fewer visits thereafter may be acceptable. However, closely monitoring symptoms and examining patients based on differences in progression rates at different sites may be important. • The incidence of progression events for OCCC peaked at 12 months after initial treatment. • Most progression events for OCCC occurred within 24 months after initial treatment. • Close follow-up for OCCC during the initial 24 months after treatment with fewer visits thereafter may be acceptable. [ABSTRACT FROM AUTHOR]

We evaluated the feasibility of completing 6 cycles of nab-paclitaxel (nab-P) and carboplatin (C) in a single arm prospective clinical trial for advanced/recurrent EC and safety and efficacy of day (D) 1, 8 nab-P in combination with D1 C q3weeks. Patients with early-stage, high-risk, advanced primary/recurrent EC without prior platinum/taxane exposure were enrolled in an open-label, single-institution trial (NCT02744898). Patients received 6 cycles of D1 nab-P 100 mg/m2 IV with C AUC 6 IV and D8 nab-P 100 mg/m2 IV q21D. The trial tested the null hypothesis that subjects completing 6 cycles was ≤0.50 versus the alternative that the proportion is ≥0.75 in a single stage design with alpha = 0.05 and power = 80% with 23 subjects. Patients who completed 6 cycles (primary outcome), objective response rate (ORR) and clinical benefit rate (CBR) were estimated with exact 95% Clopper-Pearson confidence intervals. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. From 08/2016–03/2018, 23 patients were enrolled. Nineteen patients (82.6%, 95% CI: 61.2%, 95.0%) completed 6 cycles, thus we could reject our null. Twelve patients (52.2%) experienced ≥1 grade 3/4 treatment-related adverse events including: anemia, 6 (26.1%); neutropenia, 5 (21.7%); diarrhea, 3 (13.0%). Fourteen patients (60.1%) reported grade 1 neuropathy. Of 9 patients with measurable target lesions, the ORR was 33.3% (95% CI: 7.5%, 70.1%) and CBR was 55.6% (95% CI: 21.2%, 86.3%). Median PFS in the advanced/recurrent patients was 23.2 (95% CI: 12.1, NR) months. The nab-P/C D1, 8 regimen met pre-specified feasibility criteria with acceptable toxicity and efficacy. Use of nab-P decreases need for steroid pre-medications, and this carboplatin doublet may prove advantageous for trials assessing combinations with immune checkpoint inhibitors in advanced EC. • Dose-dense nab-paclitaxel on day 1, 8 with day 1 carboplatin every 3 weeks is feasible (6-cycle completion rate of 82.6%). • In advanced/recurrent cases, median progression free survival was 23.2 months (95% CI: 12.1, not reached). • The regimen had tolerable toxicity, with 61% with grade 1 neuropathy and no patients with grade 3 or 4 neuropathy. • Nab-paclitaxel can be an acceptable taxol replacement for regimens with immunotherapy to avoid use of concomitant steroids. [ABSTRACT FROM AUTHOR]

To elucidate the clinicopathological characteristics and oncological outcomes of a special group of patients with gestational trophoblastic neoplasia (GTN) initially presenting with isolated lung lesions, elevated human chorionic gonadotropin (hCG) levels, and unobserved pelvic lesions. Overall, 2358 patients with GTN treated at our hospital between 2000 and 2023 were retrospectively reviewed, and 40 patients were evaluated. The demographic characteristics, clinicopathological features, treatment data, and follow-up information of each patient were collected. The primary outcome was progression free survival. Kaplan-Meier analysis and univariate and multivariate Cox proportional hazard analyses were used to identify the risk factors. Among the 40 patients, 95.0 % had solitary lung lesions, with a median size of 1.9 cm. Moreover, 72.5 % of patients were pathologically confirmed as epithelioid trophoblastic tumors (ETT). During a median follow-up period of 53.5 months (range, 2–143), 11 patients experienced recurrence, including all patients who received chemotherapy alone as the initial treatment, and no death was observed. Relapse treatment involved lung segmentectomy and lobectomy combined with chemotherapy and immunotherapy. Univariate and multivariate Cox analyses identified comparing with surgery±chemotherapy, chemotherapy alone as the initial treatment (hazard ratio [HR] =7.738, 95 % confidence interval [CI] 1.698–35.269, P = 0.008) as independent risk factor for recurrence. In patients with a history of pregnancy exhibiting isolated pulmonary lesions, elevated hCG levels (mostly <1000 mIU/mL), and unobserved pelvic lesions, ETT should be considered first. Surgical resection of lung lesion is crucial for optimal management. When chemotherapy is considered, multidrug regimen is recommended. • Gestational trophoblastic neoplasia (GTN) comprises a group of pregnancy-associated malignancies. • Most patients with isolated GTN of the lung had a pathological diagnosis of epithelial trophoblastic tumors (ETT). • Surgical resection of lung lesions is crucial, adjuvant and multidrug chemotherapy is recommended when needed. [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]

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]

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]

Background: Acute myeloid leukemia (AML) has a heterogeneous molecular profile, clinical presentations, and response to treatments and outcomes. DNA methylation is conducted by DNA methyltransferases including DNMT3B. Poly ADP-ribose polymerase 1 belongs to a family of enzymes that mediate important cellular processes including DNA repair, transcription, and cell death/cell proliferation, and it is involved in the development, spread, treatment, and prognosis of some cancers. The objective of this study is to assess the impact of PARP1 and DNMT3B genes expression on laboratory characteristics, response to treatment and survival in Egyptian cytogenetically normal AML patients. Methods: This study included 67 Egyptian CN-AML patients in addition to 8 healthy bone marrow donors. Measurement of DNMT3B and PARP1 gene expression was done on bone marrow samples via real-time semiquantitative polymerase chain reaction. Result: Expression of both DNMT3B and PARP1 genes was significantly upregulated in AML (P =.001, P =.036, respectively). Upregulated DNMT3B was associated with higher total leukocyte count (TLC), PB, and BM blast cell%. Also, upregulated PARP1 correlated with higher TLC, PB, and BM blast cell%. High expression of both DNMT3B and PARP1 correlated with greater frequencies of FLT3-ITD. High DNMT3B expression, and combined upregulation of both PARP1 and DNMT3B genes associated significantly with ELN stratification. But no correlation was found with response (CR), overall survival (OS), disease-free survival (DFS), or event-free survival (EFS). Conclusion: Our findings highlight the importance of considering DNMT3B and PARP1 expression levels as potential prognostic biomarkers for progression and aggressiveness of CN-AML patients in AML. Assessing their expression levels could be an indicator to guide treatment decisions and potentially improve patient outcomes. [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]