Search Results (4,802)

Background/Objectives: This study compared overall survival (OS) associated with common real-world treatment sequences in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in the United States. Methods: Utilizing the nationwide Flatiron Health electronic health record-derived de-identified database, adult CLL/SLL patients who initiated systemic therapy (JAN2016-NOV2023) and received at least two lines of therapy (LoTs) were analyzed. Treatment regimens were categorized based on drug class, and most frequent (n ≥ 50) sequences (first LoT followed by [→] second LoT) were compared. OS from initiation of the first LoT was compared using multivariable Cox proportional hazard models, and adjusted hazard ratios with 95% CIs were reported. Results: Among 2354 eligible patients, n = 1711 (73%) received the 16 most frequent treatment sequences. Sequencing chemoimmunotherapy (CIT) → CIT (HR: 2.29 [1.23–4.28]), anti-CD20 monoclonal antibody (anti-CD20mab) monotherapy → CIT (1.95 [1.03–3.69]), and covalent Bruton tyrosine kinase inhibitor (cBTKi) monotherapy → anti-CD20mab monotherapy (2.00 [1.07–3.74]) were associated with worse OS compared to patients treated with cBTKi monotherapy → B-cell lymphoma 2 inhibitors (BCL2i) + anti-CD20mab (reference). Conclusions: OS associated with other sequences were not significantly different from the reference sequence in adjusted analyses, suggesting a lack of evidence for the optimal standard of care for sequencing the first two LoTs in real-world settings. Future research should reassess sequencing outcomes as novel treatments become adopted into clinical practice. Full article

Background/Objectives: Neoadjuvant radiochemotherapy and perioperative chemotherapy are both well-established treatment strategies for locally advanced adenocarcinoma of the esophagus (EAC) and the esophagogastric junction (AEGJ). However, recent knowledge controversially discusses whether neoadjuvant radiotherapy or perioperative chemotherapy represents superior therapeutic options to prolong survival or cause less toxicity. Methods: We retrospectively analyzed 76 patients with locally advanced EAC or AEGJ treated at our tertiary cancer center between January 2015 and March 2023. Patients received either perioperative FLOT chemotherapy (n = 36) or neoadjuvant radiochemotherapy following the CROSS protocol (n = 40), followed by surgical resection and standardized follow-up. We compared survival outcomes, toxicity profiles, treatment compliance, and surgical results between the two groups. Results: There were no statistically significant differences between FLOT and CROSS treatments in five-year loco-regional controls (LRC: 61.5% vs. 68.6%; p = 0.81), progression-free survival (PFS: 33.9% vs. 42.8%; p = 0.82), overall survival (OS: 60.2% vs. 63.4%; p = 0.91), or distant controls (DC: 42.1% vs. 56.5%; p = 0.39). High-grade hematologic toxicities did not significantly differ between groups (p > 0.05). Treatment compliance was lower in the FLOT group, with 50% (18/36) not completing all the planned chemotherapy cycles, compared to 17.5% (7/40) in the CROSS group. All the patients in the CROSS group received the full radiotherapy dose. Surgical outcomes and post-surgical tumor status were comparable between the groups. Conclusions: Although perioperative chemotherapy with FLOT has recently become a standard of care for locally advanced EAC and AEGJ, neoadjuvant radiochemotherapy per the CROSS protocol remains a well-tolerated alternative. In appropriately selected patients, both approaches yield comparable oncological outcomes. Full article

Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and safety of GCD treatment for advanced biliary tract cancer in real-world conditions. Methods: The study subjects were 52 patients with biliary tract cancer who received GCD therapy between January 2023 and May 2024. The observation parameters included the modified Glasgow Prognostic Score (mGPS), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), tumor markers (CEA, CA19-9), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: The cohort included 36 men and 16 women, with a median age of 73.0 years. There were 36 cases of cholangiocarcinoma (distal: 10, perihilar: 19, intrahepatic: 7), 13 cases of gallbladder cancer, and 3 cases of ampullary carcinoma. The stages were locally advanced in 30 cases and metastatic in 22 cases. Biliary drainage was performed in 30 cases. There were 38 cases receiving first-line therapy and 14 cases receiving second-line or later treatments. The median values at the start of GCD therapy were ALB 3.7 g/dL, CRP 0.39 mg/dL, NLR 2.4, PLR 162.5, CEA 4.8 ng/mL, and CA19-9 255.9 U/mL. The mGPS distribution was 0:23 cases, 1:18 cases, and 2:11 cases. The treatment outcomes were ORR 25.0% (CR 2 cases, PR 11 cases), DCR 78.8% (SD 28 cases, PD 10 cases, NE 1 case), median PFS 8.6 months, and median OS 13.9 months. The PLR was suggested to be useful for predicting PFS. A decrease in CEA at six weeks after the start of treatment was a significant predictor of PFS and OS. Gallbladder cancer had a significantly poorer prognosis compared to other cancers. The immune-related adverse events included hypothyroidism in two cases, cholangitis in one case, and colitis in one case. Conclusions: The ORR, DCR, and PFS were comparable to those in the TOPAZ-1 trial. Although limited by its retrospective design and small sample size, this study suggests that GCD therapy is an effective treatment regimen for unresectable biliary tract cancer in real-world clinical practice. Full article

Background: Pancreatic adenocarcinoma (PDAC) with liver oligometastases (LOM) presents a therapeutic challenge, with optimal management strategies remaining uncertain. This study evaluates the long-term outcomes, patterns of disease progression, and potential factors influencing prognosis in this patient subset. Methods: Patients diagnosed with PDAC and LOM were retrospectively analyzed. Disease progression patterns, causes of death, and predictors of long-term outcomes were assessed. Results: Among 1442 patients diagnosed with metastatic PDAC between November 2009 and July 2024, 129 (9%) presented with LOM, defined as ≤3 liver lesions each measuring <2 cm. Patients with LOM had significantly improved overall survival (OS) compared to those with high-burden disease (p = 0.026). The cause of death (local regional disease vs. systemic disease) could be determined in 74 patients (57%), among whom age at diagnosis, history of smoking, and white blood cell (WBC) count differed significantly between groups. However, no significant difference in OS was observed between the two groups (p = 0.64). Sixteen patients (22%) died from local complications of the primary tumor, including 6 patients (7%) who showed no evidence of new or progressive metastases. In competing risk and multivariable analysis, a history of smoking remained the only factor significantly associated with death due to local complications. Conclusions: Approximately one in five patients with PDAC-LOM died from local tumor-related complications—some without metastatic progression—highlighting a potential role for surgical intervention. Further multicenter studies are warranted to refine diagnostic criteria and better identify patients who may benefit from surgery. Full article

Background/Objectives: The quality of surgical margins has been shown to be a prognostic factor in many sarcoma entities, yet its role in osteosarcoma remains controversial. While previous studies have shown that the outcome was not related to the margin width in bone, the impact of the extraosseous margin width (margin at the soft tissue invasion)—which needs to be close sometimes due to neurovascular structures—needs to be assessed. This study aims to evaluate the influence of soft tissue surgical margins on local recurrence and overall survival in patients with high-grade osteosarcoma. Methods: We conducted a retrospective, single-center study including 75 patients treated for high-grade osteosarcoma. All patients underwent standardized neoadjuvant chemotherapy followed by complete surgical resection. Patients were stratified into three groups based on the histological margin width of the extraosseous parts: group 1 (<1 mm), group 2 (1–5 mm), and group 3 (≥5 mm). Primary endpoints were local recurrence and overall survival (OS), analyzed using Kaplan–Meier estimates, log-rank tests, and Cox regression. Results: Local recurrence occurred in seven patients (9%). Although the overall comparison between the three groups was not statistically significant (p = 0.074), a subgroup analysis revealed a significantly higher recurrence rate in patients with margins < 1 mm compared to those with wider margins (p = 0.024). No significant differences in overall survival (OS) were observed between the groups (p = 0.896). Tumor location, metastatic status, and UICC stage were significant predictors for both endpoints in univariate analysis. However, none of these association were confirmed in multivariate analyses. Conclusions: Very close surgical margins (<1 mm) may increase the risk of local recurrence in high-grade osteosarcoma; however, they do not appear to affect overall survival. Full article

Background/Objectives: This single-cohort follow-up study describes the median overall survival (OS) in patients with unresectable head and neck squamous cell carcinoma (HNSCC) due to invasion of vital structures, which is under-represented in the current literature. Secondarily, subgroups were evaluated according to the type of presentation, in order to identify clinical characteristics and contribute to developing an appropriate treatment plan and managing patient’s expectations. Methods: This single-cohort observational study analysed the OS of 39 patients from the Otolaryngology Department with advanced-stage head and neck cancer with invasion of vital anatomical structures considered ineligible for surgical treatment. Secondarily, subgroups were evaluated according to type of presentation and various clinical characteristics. Results: A total of 39 patients radiologically classified as having unresectable HNSCC (i.e., unsuitable for surgical resection), with a mean age of 66.87 years, were included during a 24-month follow-up. By the end of the study, 56.4% of the patients had died. The median OS was 16.09 months. Statistically significant differences were observed when comparing human papilloma virus (HPV)-positive and -negative status and when comparing initial and recurrent tumours. Conclusions: The invasion of anatomical structures such as the skull base, internal carotid artery, and prevertebral space was associated with a marked decrease in survival, with an OS time of 16 months. This study provides valuable evidence in patients with unresectable HNSCC, highlighting tumour recurrence and HPV-negative status as important indicators of poor prognosis. Full article

Transcription factors play crucial roles in regulating gene expression, and any dysregulation in their levels could be involved in cancer progression. The role of androgen receptors (AR) and zinc finger (ZNF) proteins in tumors, like prostate cancer (PC), remains poorly understood. Moreover, due to the multifaceted transcriptional behavior of ARs and ZNFs, their biological role in cancer progression may also depend on the interplay with micro-RNAs (miRNAs). Based on The Cancer Genome Atlas (TCGA) database, we analyzed the expression levels of zinc finger transcripts and ARs in PC. Specifically, exploring their involvement in cancer progression and regulation by miRNAs. The analysis relied on several tools to create a multivariate combination of the original biomarkers to improve their diagnostic efficacy. Multidimensional Scaling (MDS) identified two new dimensions that were entered into a regression analysis to determine the best predictors of overall survival (OS) and disease-free interval (DFI). A combination of both dimensions predicted almost 50% (R² = 0.46) of the original variance of OS. Kaplan–Meier survival analysis also confirmed the significance of these two dimensions regarding the clinical output. This study showed preliminary evidence that several transcription factor expression levels belonging to the zinc family and related miRNAs can effectively predict patients’ overall PC survivability. Full article

Background: Pleural mesothelioma (PM) is a type of cancer that is difficult to diagnose and treat. Patients may have vastly varying prognoses, and prognostic factors may help guide the clinical approach. As a recently identified biomarker, the pan-Immune-Inflammation-Value (PIV) is a simple, comprehensive, and peripheral blood cell-based biomarker. Methods: The present study represents a retrospective observational analysis carried out within a single-center setting. Ninety-five patients with PM stages I–IV were enrolled in the study. We analyzed the correlation between patients’ demographic characteristics, clinicopathological factors such as histological subtypes, surgery status, tumor thickness, blood-based parameters, and treatment options with their prognoses. PIV was calculated by the following formula: (neutrophil count × monocyte count × platelet count)/lymphocyte count. Additionally, blood-based parameters were used to calculate the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII). Results: We categorized the patients into two groups, low PIV group (PIV ≤ 732.3) and high PIV group (PIV > 732.3) according to the determined cut-off value, which was defined as the median. It was revealed that high PIV was associated with poor survival outcomes. The median follow-up period was 15.8 months (interquartile range, IQR, 7.1 to 29.8 months). The median overall survival (OS) was significantly longer in patients in the low PIV group (median 29.8 months, 95% confidence interval (CI), 15.6 to 44) than the high PIV group (median 14.7 months, 95% CI, 10.8 to 18.6 p < 0.001). Furthermore, the study revealed that patients with low PIV, NLR, and SII values were more likely to be eligible for surgery and were diagnosed at earlier stages. Additionally, these markers were identified as potential predictors of disease-free survival (DFS) in the surgical cohort and of treatment response across the entire patient population. Conclusions: In addition to well-established clinical factors such as stage, histologic subtype, resectability, and Eastern Cooperative Oncology Group (ECOG) performance status (PS), PIV emerged as an independent and significant prognostic factor of overall survival (OS) in patients with PM. Moreover, PIV also demonstrated a remarkable independent prognostic value for disease-free survival (DFS) in this patient population. Additionally, some clues are provided for conditions such as treatment responses, staging, and suitability for surgery. As such, in this cohort, it has outperformed the other blood-based markers based on our findings. Given its ease of calculation and cost-effectiveness, PIV represents a promising and practical prognostic tool in the clinical management of pleural mesothelioma. It can be easily calculated using routinely available laboratory parameters for every cancer patient, requiring no additional cost or complex procedures, thus facilitating its integration into everyday clinical practice. Full article

Background: Delays in breast cancer treatment negatively affect prognosis and have increased over time. Data on waiting times in Switzerland are limited. Patients and Methods: This study analyzed cancer registry data from 2003 to 2005 (2628 patients) and 2015 to 2017 (421 patients) to evaluate waiting times for diagnosis, surgery, and radiotherapy; temporal trends; and survival in women with stage I–III invasive breast cancer treated with surgery without chemotherapy. Associations with demographic/clinical factors and overall survival (OS) were assessed using ANOVA, uni-/multivariable regression, Kaplan–Meier, and Cox regression. Results: From 2003 to 2005, mean intervals were biopsy-to-diagnosis 4.3 days, diagnosis-to-surgery 18.8 days, biopsy-to-surgery 26.8 days, and surgery-to-radiotherapy 56.7 days. Longer diagnosis-to-surgery times were associated with metropolitan areas, public hospitals, basic insurance, mastectomy, and older age (all p < 0.001). Radiotherapy delays were also longer in metropolitan areas and after mastectomy (p < 0.001). Between 2003–2005 and 2015–2017, diagnosis-to-surgery times rose in Eastern Switzerland (from 21.3 to 31.2 days), while radiotherapy timing remained stable. Five-year overall survival improved (from 76.7% to 88.4%), but was not significantly impacted by diagnosis-to-surgery intervals. Conclusions: Despite timely surgery in Switzerland (2003–2005), disparities existed, and time to surgery increased by 2015–2017. Reducing waiting times remains important despite no significant short-term OS impact. Full article

Prostate cancer accounts for approximately 1.5 million new diagnoses and 400,000 deaths every year worldwide, and demographic projections indicate a near-doubling of both figures by 2040. Despite existing treatments, 10–20% of patients eventually progress to metastatic castration-resistant disease (mCRPC). The median overall survival (OS) after progression to mCPRC drops to 24 months, and efficacy drops severely after each additional line of treatment. Omics platforms have reached advanced levels and enable the acquisition of high-resolution large datasets that can provide insights into the molecular mechanisms underlying PCa pathology. Genomics, especially DDR (DNA damage response) gene alterations, detected via tissue and/or circulating tumor DNA, efficiently guides therapy in advanced prostate cancer. Given recent developments, we have performed a comprehensive literature search to cover recent research and clinical trial reports (over the last five years) that integrate omics along three converging trajectories in therapeutic development: (i) predicting response to approved agents with demonstrated survival benefits, (ii) stratifying patients to receive therapies in clinical trials, (iii) guiding drug development as part of drug repurposing frameworks. Collectively, this review is intended to serve as a comprehensive resource of recent advancements in omics-guided therapies for advanced prostate cancer, a clinical setting with existing clinical needs and poor outcomes. Full article

Background: Angiosarcomas (ASs) represent a heterogeneous and highly aggressive subset of tumors that respond poorly to systemic treatments and are associated with short progression-free survival (PFS) and overall survival (OS). The aim of this study was to develop and validate an immune-related prognostic model—termed the AS score—using data from two independent sarcoma cohorts. Methods: A prognostic model was developed using a previously characterized cohort of 25 angiosarcoma samples. Candidate genes were identified via the Maxstat algorithm (Maxstat v0.7-25 for R), combined with log-rank testing. The AS score was then computed by weighing normalized gene expression levels according to Cox regression coefficients. For external validation, transcriptomic data from TCGA Sarcoma cohort (n = 253) were analyzed. The Immunoscore—which reflects the tumor immune microenvironment—was inferred using the ESTIMATE package (v1.0.13) in R. All statistical analyses were performed in RStudio (v 4.0.3). Results: Four genes—IGF1R, MAP2K1, SERPINE1, and TCF12—were ultimately selected to construct the prognostic model. The resulting AS score enabled the classification of angiosarcoma cases into two prognostically distinct groups (p = 0.00012). Cases with high AS score values, which included both cutaneous and non-cutaneous forms, exhibited significantly poorer outcomes, whereas cases with low AS scores were predominantly cutaneous. A significant association was observed between the AS score and the Immunoscore (p = 0.025), with higher Immunoscore values found in high-AS score tumors. Validation using TCGA sarcoma cohort confirmed the prognostic value of both the AS score (p = 0.0066) and the Immunoscore (p = 0.0029), with a strong correlation between their continuous values (p = 2.9 × 10⁻⁸). Further survival analysis, integrating categorized scores into four groups, demonstrated robust prognostic significance (p = 0.00021). Notably, in tumors with a low Immunoscore, AS score stratification was not prognostic. In contrast, among cases with a high Immunoscore, the AS score effectively distinguished outcomes (p < 0.0001), identifying a subgroup with poor prognosis but potential sensitivity to immunotherapy. Conclusions: This combined classification using the AS score and Immunoscore has prognostic relevance in sarcoma, suggesting that angiosarcomas with an immunologically active microenvironment (high Immunoscore) and poor prognosis (high AS score) may be prime candidates for immunotherapy and this approach warrants prospective validation. Full article

Pediatric high-grade glioma (pHGG) is a devastating group of childhood cancers associated with poor outcomes. Traditionally, diagnosis was based on histologic and immunohistochemical characteristics, including high mitotic activity, presence of necrosis, and presence of glial cell markers (e.g., GFAP). With advances in molecular tumor profiling, these tumors have been recategorized based on specific molecular findings that better lend themselves to prediction of treatment response and prognosis. pHGG is now categorized into four subtypes: H3K27-altered, H3G34-mutant, H3/IDH-WT, and infant-type high-grade glioma (iHGG). Molecular profiling has not only increased the specificity of diagnosis but also improved prognostication. Additionally, these molecular findings provide novel targets for individual tumor-directed therapy. While these therapies are largely still under investigation, continued investigation of distinct molecular markers in these tumors is imperative to extending event-free survival (EFS) and overall survival (OS) for patients with pHGG. Full article

High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer, accounting for approximately 70% of cases. This study investigates genetic mutations and their associations with overall survival (OS), complete cytoreduction (R0), and platinum response in patients undergoing either primary debulking surgery followed by adjuvant chemotherapy (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (NACT). Genetic analysis was performed on 43 primary HGSOC tumor samples using targeted massive parallel sequencing via next-generation sequencing (NGS). Clinical and molecular data were evaluated collectively and through subgroup comparisons between PDS and NACT cohorts. All analyzed samples harbored genetic alterations. Univariate survival analysis revealed that the total number of mutations (p = 0.0035), as well as mutations in HRAS (p = 0.044), FLT3 (p = 0.023), TP53 (p = 0.03), and ERBB4 (p = 0.007), were significantly associated with poorer OS. Multivariate Cox regression integrating clinical and molecular data confirmed that ERBB4 mutations are independently associated with adverse outcomes. These findings reveal a distinctive mutational landscape between the PDS and NACT groups and suggest that ERBB4 alterations may define a particularly aggressive tumor phenotype. This study contributes to a deeper understanding of HGSOC biology and may support the development of novel therapeutic targets and personalized treatment strategies in the context of precision oncology. Full article

Background: Lung cancer remains the leading cause of cancer-related mortality worldwide. Advances in screening, diagnosis, and management have transformed clinical practice, particularly with the integration of immunotherapy and target therapies. Methods: A systematic literature search was carried out for the period between October 2016 to September 2024. Phase II and III randomized trials evaluating ICI monotherapy, ICI–chemotherapy combinations, and dual ICI regimens in patients with advanced NSCLC were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (AEs). Results: PD-1-targeted therapies demonstrated superior OS compared to PD-L1-based regimens, with cemiplimab monotherapyranking highest for OS benefit (posterior probability: 90%), followed by sintilimab plus platinum-based chemotherapy (PBC) and pemetrexed—PBC. PFS atezolizumab plus bevacizumab and PBC, and camrelizumab plus PBC were the most effective regimens. ICI–chemotherapy combinations achieved higher ORRs but were associated with greater toxicity. The most favorable safety profiles were observed with cemiplimab, nivolumab, and avelumab monotherapy, while atezolizumab plus PBC and sugemalimab plus PBC carried the highest toxicity burdens. Conclusions: In PD-L1-unselected advanced NSCLC, PD-1 blockade—particularly cemiplimab monotherapy—and rationally designed ICI–chemotherapy combinations represent the most efficacious treatment strategies. Balancing efficacy with safety remains critical, especially in the absence of predictive biomarkers. These findings support a patient-tailored approach to immunotherapy and highlight the need for further biomarker-driven and real-world investigations to optimize treatment selection. Full article

CAPOX and FOLFOX are widely used chemotherapy regimens for colorectal cancer (CRC). The superiority of one regimen over the other in a real-world setting (RWE) could have significant clinical implications given their common use, but such RWE is limited. This study analyzed provincial database records of 13,461 Canadian patients treated from 2005 to 2017. The primary outcomes were rates of Emergency Department visits and/or hospitalizations (ED/H) and overall survival (OS). CAPOX was used less frequently (8.4%) than FOLFOX (91.6%), often in older patients (p < 0.003 for Stage I–III; p < 0.001 for Stage IV). CAPOX recipients had shorter treatment durations (median 15 vs. 20 weeks, p = 0.002) and higher unadjusted ED/H rates (60.8% vs. 50.9%, p < 0.001), though this difference was nonsignificant on multivariate analysis (MVA) (HR 1.05 (0.92, 1.20), p = 0.466). Patients receiving CAPOX had worse OS than those on FOLFOX, (5-year OS 70.1% vs. 77.2% (p < 0.001) non-metastatic; 16.6% vs. 33.2% (p < 0.001) metastatic). MVA confirmed inferior OS with CAPOX (HR 1.42, p < 0.001). Other predictors of shorter OS included older age, male sex, comorbidities, rural residence, and lower income. This administrative data is at risk of bias but highlights the need for careful patient selection and informed treatment decision making. Full article