INTRODUCTION: This systematic review and meta-analysis evaluated whether compression therapy prevents chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer patients receiving taxanes. METHODS: Randomized con...INTRODUCTION: This systematic review and meta-analysis evaluated whether compression therapy prevents chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer patients receiving taxanes. METHODS: Randomized controlled trials (RCTs) including breast cancer patients treated with taxanes and reporting CTCAE-graded CIPN were eligible. The primary outcome was grade ≥2 CIPN incidence. Odds ratios (OR) were pooled with a random-effects model; heterogeneity was assessed with I, and bias with the Cochrane RoB 2.0 tool. RESULTS: Three RCTs ( = 195) met criteria. Pooled analysis showed compression therapy significantly lowered CIPN incidence versus control (OR 0.33, 95% CI 0.15-0.71, = 0.004; I = 31%). Compared with standard care, compression markedly reduced CIPN (OR 0.24, 95% CI 0.11-0.49, = 0.0001). No significant benefit was observed versus sham compression (OR 0.76, 95% CI 0.23-2.54, = 0.66). CONCLUSIONS: Compression therapy reduced grade ≥2 CIPN in breast cancer patients receiving taxanes, with benefits over standard care but not sham compression, suggesting placebo contributions. Limitations include the small number of available trials and participants. Larger, rigorously sham-controlled studies are required to confirm effectiveness and establish standardized timing and pressure protocols. REGISTRATION: PROSPERO (CRD420251055184).
BACKGROUND: Patients with advanced EGFR-mutant NSCLC and high PD-L1 expression (TPS ≥50%) typically respond poorly to EGFR-TKI monotherapy. We compared EGFR-TKI plus chemotherapy versus TKI alone in this population. RESE...BACKGROUND: Patients with advanced EGFR-mutant NSCLC and high PD-L1 expression (TPS ≥50%) typically respond poorly to EGFR-TKI monotherapy. We compared EGFR-TKI plus chemotherapy versus TKI alone in this population. RESEARCH DESIGN AND METHODS: This retrospective study included 212 patients receiving first-line osimertinib with chemotherapy ( = 98) or as monotherapy ( = 114). Primary endpoint was progression-free survival (PFS). RESULTS: Combination therapy significantly improved median PFS overall (22.5 vs 13.8 months; HR = 0.513, 95% CI:0.372-0.803; < 0.001) and in PD-L1-high patients (18.2 vs 7.9 months; HR = 0.356, 95% CI:0.195-0.641; = 0.001). ORR was higher with combination therapy (67.3% vs 36.8%; < 0.001). Grade ≥3 adverse events were more common with combination therapy (45.9% vs 22.8%) but were primarily manageable hematological events. CONCLUSIONS: Osimertinib-chemotherapy combination showed superior efficacy versus monotherapy in EGFR-mutant, PD-L1-high NSCLC, with manageable safety. Our real-world findings validate and extend the FLAURA2 results by highlighting this high-risk subgroup as one that may derive particular benefit from first-line combination therapy.
INTRODUCTION: Intravesical sequential gemcitabine - docetaxel (Gem/Doce) has emerged as an important chemotherapeutic regimen in the management of non - muscle-invasive bladder cancer (NMIBC). It holds particular clinica...INTRODUCTION: Intravesical sequential gemcitabine - docetaxel (Gem/Doce) has emerged as an important chemotherapeutic regimen in the management of non - muscle-invasive bladder cancer (NMIBC). It holds particular clinical significance in the context of high-risk NMIBC (HR-NMIBC) that either fails standard Bacillus Calmette - Guérin (BCG) immunotherapy or when BCG is contraindicated or unavailable. The combination leverages two cytotoxic agents with complementary mechanisms to achieve tumor eradication while aiming to preserve the bladder. AREAS COVERED: This review explores the evidence for the use of intravesical Gem/Doce in NMIBC. We performed a scoping review of studies across BCG-naïve and BCG-unresponsive populations (MEDLINE, Embase, ClinicalTrials.gov; 2015-2025). Outcomes assessed included efficacy, adverse events, safety, and bladder preservation. We also discuss emerging data on novel delivery methods, maintenance strategies and combination regimens. EXPERT OPINION: Intravesical Gem/Doce has transitioned from an experimental salvage approach to a promising mainstream option in NMIBC management. Current evidence indicates that intravesical Gem/Doce can achieve durable disease control in a substantial proportion of patients with HR-NMIBC, offering a well-tolerated and cost-effective bladder-sparing strategy. While the absence of randomized trials means Gem/Doce is not yet a formal standard of care, the accumulating clinical experience and supportive outcomes have led to its inclusion in contemporary treatment algorithms.
INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) is a malignancy with a significant recurrence and progression risk. While intravesical Bacillus Calmette-Guérin (BCG) has remained the standard of care for decades...INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) is a malignancy with a significant recurrence and progression risk. While intravesical Bacillus Calmette-Guérin (BCG) has remained the standard of care for decades, limitations in efficacy, tolerability, and global supply underscore the need for novel therapeutic strategies. Many patients relapse after BCG and are offered radical cystectomy, a highly morbid operation which some are unfit for or decline. Immune checkpoint inhibitors (ICIs) have revolutionized neoadjuvant and advanced bladder cancer therapy. This has driven interest in ICIs as bladder-sparing alternatives in BCG-unresponsive high-risk NMIBC (HR-NMIBC). AREAS COVERED: This scoping review (MEDLINE, Embase, ClinicalTrials.gov; 2015-2025) explores the emerging role of ICIs in NMIBC. It summarizes data from completed and ongoing trials in both BCG-naïve and BCG-unresponsive settings, highlighting key efficacy and safety outcomes. Special emphasis is given to combination approaches and novel delivery routes. EXPERT OPINION: Checkpoint inhibition represents a potentially transformative advance in the bladder-sparing management of NMIBC, particularly in patients unfit for or refusing radical cystectomy. However, widespread adoption will require robust phase III data combined with optimal patient selection to temper concerns regarding toxicity and cost. Ongoing research into combination regimens and local delivery may refine risk-benefit profiles and personalize treatment in the near future.
INTRODUCTION: Lung cancer remains the leading cause of cancer-related mortality, and reliable prognostic biomarkers are needed. The prognostic significance of myeloid-derived suppressor cells (MDSCs) in lung cancer is th...INTRODUCTION: Lung cancer remains the leading cause of cancer-related mortality, and reliable prognostic biomarkers are needed. The prognostic significance of myeloid-derived suppressor cells (MDSCs) in lung cancer is the aim of the current systematic review and meta-analysis. METHODS: A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase, and eligible studies included patients with lung cancer reporting survival/progression outcomes by MDSCs level. Study quality was assessed using the Joanna Briggs Institute (JBI) checklist. The Comprehensive Meta-Analysis (CMA) software version 3 was used to estimate pooled hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Twenty-five studies (1,679 patients) were included. Elevated baseline monocytic MDSCs (M-MDSCs) were significantly associated with worse overall survival (OS) in non-small cell lung cancer (NSCLC) (HR = 1.89, 95% CI: 1.39-2.59) and small cell lung cancer (SCLC) (HR = 2.72, 95% CI: 1.62-4.59), and with shorter progression/recurrence-free survival in NSCLC (HR = 1.86, 95% CI: 1.44-2.40). Associations for polymorphonuclear MDSCs (PMN-MDSCs) were weaker and inconsistent, showing significance only in HR for OS based on univariable data (HR = 1.76, 95% CI: 1.32-2.35). CONCLUSIONS: High M-MDSCs predict adverse outcomes in lung cancer, supporting their role as prognostic biomarkers and potential therapeutic targets. REGISTRATION: PROSPERO (CRD420251026405).
BACKGROUND: To explore Ubiquitin D (UBD) and autophagy in hepatocellular carcinoma (HCC) and the key role of Olaparib targeting UBD in treating HCC. RESEARCH DESIGN AND METHODS: Bioinformatics analysis was conducted to s...BACKGROUND: To explore Ubiquitin D (UBD) and autophagy in hepatocellular carcinoma (HCC) and the key role of Olaparib targeting UBD in treating HCC. RESEARCH DESIGN AND METHODS: Bioinformatics analysis was conducted to study UBD expression in HCC tissues. qRT-PCR and Western blot measured UBD mRNA/protein levels, autophagy markers, and Gln metabolism proteins in HCC tissues. Cellular thermal shift assay (CETSA) confirmed Olaparib-UBD interaction. A xenograft tumor model was established to observe tumor growth in mice, with qRT-PCR and western blot used to measure UBD expression levels in tumor tissues and Immunohistochemistry (IHC) used to assess expression of Microtubule-associated protein light chain 3 (LC3), sequestosome 1 (P62), solute carrier family 1 member 5 (SLC1A5), and glutaminase (GLS). RESULTS: UBD was highly expressed in HCC tissues ( = 7.6e-11). UBD could negatively regulate autophagy levels by activating Gln metabolism. Olaparib could target and downregulate UBD expression, promoting HCC cell autophagy by regulating Gln metabolism pathways. Olaparib treatment in xenograft mice overexpressing UBD significantly reduced tumor growth ( < 0.05), inhibited Gln metabolism pathways, and enhanced HCC cell autophagy. CONCLUSIONS: Olaparib targeted UBD to promote autophagy in HCC by inhibiting Gln metabolism pathways.
BACKGROUND: This subgroup analysis investigates the clinical characteristics, treatment patterns, and outcomes of chronic lymphocytic leukemia (CLL) in the Middle East (ME). RESEARCH DESIGN AND METHODS: Retrospective stu...BACKGROUND: This subgroup analysis investigates the clinical characteristics, treatment patterns, and outcomes of chronic lymphocytic leukemia (CLL) in the Middle East (ME). RESEARCH DESIGN AND METHODS: Retrospective study retrieved medical records of CLL patients treated for ≥12 months (CLL-treated) or treatment-naïve (TN). Results included data from 442 CLL-treated and 123 TN patients across five ME countries. RESULTS: CLL-treated group mean age: 61.1 ± 11.28 years; TN cohort: 63.5 ± 13.53 years. Most patients in both groups were male. CLL-IPI scores were mostly unavailable in both cohorts. Cytogenetic abnormalities were tested in 20.6% of CLL-treated and 18.7% of TN cohorts, with del(17p) being the most common abnormality (12.4% and 11.4%, respectively). TP53 aberrations were found in 9.0% of CLL-treated and 9.8% of TN cohorts. Regarding first-line treatment, 76.5% received CIT, while 17.9% received targeted therapies, with ibrutinib (75.9%) being the most common. CIT use led to significant resource utilization, including outpatient visits, length of stay, and blood transfusions. CONCLUSION: CLL management in the ME is characterized by suboptimal utilization of risk-based treatment and genetic testing despite access to targeted therapy. Poor CLL outcomes stem from reliance on CIT, associated with an unfavorable safety profile and healthcare resource use compared to targeted therapies in the region. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is
INTRODUCTION: Oncolytic viruses (OVs) are a promising yet understudied class of therapeutic agents. OVs mediate anti-tumor activity through multiple mechanisms, including direct lysis of tumor cells, local expression of...INTRODUCTION: Oncolytic viruses (OVs) are a promising yet understudied class of therapeutic agents. OVs mediate anti-tumor activity through multiple mechanisms, including direct lysis of tumor cells, local expression of therapeutic transgenes, and induction of anti-tumor immunity. In 2015, Talimogene laherparepvec (T-VEC) was approved OV for melanoma. Recent literature search and real-world experience have highlighted some of the challenges with clinical adoption of OV therapy and identified new opportunities for improving the clinical use of OVs for cancer treatment. AREAS COVERED: This review provides a brief overview of recent challenges and lessons learned from clinical trials and real-world data related to T-VEC and explores novel strategies for enhancing the therapeutic activity of OVs. EXPERT OPINION: OVs are versatile agents that can attack cancer at multiple levels. The ability to use OVs to add to defined mechanisms of anti-tumor activity, such as direct tumor cell killing, induction of anti-viral and anti-tumor immune responses, and effective delivery of therapeutic payloads, have resulted in multiple new OVs with promising early clinical data. OVs can be an especially useful tool for developing a more personalized approach to cancer treatment based on unique clinical features of patients and the molecular features of specific tumors.
Pelosi G, Laffi A, Catalano G
… +16 more, Bruno A, Papotti M, Bassani B, Bianchi F, Duregon E, De Pas TM, Catania C, Ricotta R, Papa R, Harari S, Sonzogni A, Guerriero I, Ambrosino C, Pane K, Franzese M, Gemelli M
INTRODUCTION: Neuroendocrine neoplasms (NENs) of the lung make up a heterogeneous clinicopathologic ensemble, encompassing well-differentiated neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Despite be...INTRODUCTION: Neuroendocrine neoplasms (NENs) of the lung make up a heterogeneous clinicopathologic ensemble, encompassing well-differentiated neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Despite being characterized since decades, they still continue to embody diagnostic and therapeutic challenges, where establishing correlations among tumor nomenclature, molecular alterations, and therapeutic options is essential for the best clinical decision making. AREAS COVERED: Lung NENs were dissected according to five conveying perspectives (available English literature in PubMed, National Library of Medicine): (i) pathologic and molecular grounds for clinical decision making; (ii) tumor microenvironment and tumor immune microenvironment; (iii) how to manage NETs, especially in the metastatic setting; iv) handling life-threatening NECs, especially in light of emerging therapeutic protocols; (v) radiotherapy with some hints at the surgery's role. EXPERT OPINION: Diagnosis of NETs and NECs has precise clinical implications, which influences tumor nomenclature and clinical decision making (surgery, chemotherapy, radiotherapy, immuno-oncology). However, unexpected subtypes are currently emerging, which question the traditional segregation of NETs and NECs as separate and non-communicating tumor subsets, with no pathogenetic link. This paradigm shift could not only affect our outlook on lung NENs, but even modify the essence of the patient clinical management.
INTRODUCTION: Neuroplasticity is a dynamic process by which the brain reorganizes its structure and function in response to internal and external stimuli. In patients with brain neoplasms, neuroplasticity is crucial for...INTRODUCTION: Neuroplasticity is a dynamic process by which the brain reorganizes its structure and function in response to internal and external stimuli. In patients with brain neoplasms, neuroplasticity is crucial for preserving or restoring function, as it enables compensation for the tumor-induced disruption of neuronal circuits. Understanding this adaptive capacity is vital for improving clinical outcomes. AREAS COVERED: This review examines current research on neuroplasticity in the context of brain tumors. It explores how factors such as tumor location, molecular and genetic profiles, cognitive reserve, and DNA repair capacity influence neural adaptation. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science, focusing on studies related to neuroplasticity, connectome analysis, and artificial intelligence (AI) in neuro-oncology. The application of connectomics is discussed as a means to assess brain network reorganization. Furthermore, the integration of AI is analyzed concerning its potential in enhancing diagnostic precision, prognostic models, and individualized treatment strategies. EXPERT OPINION: The convergence of neuroplasticity research, connectomics, and AI offers promising avenues for advancing personalized neuro-oncology care. Greater understanding of these elements can guide clinicians in developing tailored therapeutic interventions, ultimately improving patient function, prognosis, and quality of life.
INTRODUCTION: Peripheral neuropathy is a well-known complication in patients undergoing taxane chemotherapy. Several measures to prevent this condition have been tried, but none have yielded conclusive results. METHODS:...INTRODUCTION: Peripheral neuropathy is a well-known complication in patients undergoing taxane chemotherapy. Several measures to prevent this condition have been tried, but none have yielded conclusive results. METHODS: MEDLINE, Embase, Cochrane, and Web of Science databases were searched for randomized (RCTs) and self-controlled (SCTs) trials comparing cryotherapy with standard care in patients with breast cancer undergoing taxane-based chemotherapy and reporting any of the following outcomes: (1) chemotherapy-induced peripheral neuropathy (CIPN) or (2) adverse events. RESULTS: A total of 395 patients from 10 studies were included, all female. The age of participants ranged from 49.8 to 56.1 years. Incidence of any-grade CIPN was not significantly different between groups (RCTs RR 0.59; 95% CI 0.21-1.66; = 0.320; SCTs RR 0.40; 95% CI 0.10-1.62; = 0.198). No difference was observed in adverse events leading to discontinuation of cryotherapy (RCTs RR 0.72; 95% CI 0.17-3.05; = 0.660; SCTs RR 1.09; 95% CI 0.51-2.34; = 0.821). CONCLUSIONS: Cryotherapy was not statistically superior to the standard of care in reducing CIPN, without an increased risk of adverse events leading to discontinuation of cryotherapy. These findings underscore the need for further studies with more rigorous methodologies to definitively validate or rule out this finding. REGISTRATION: PROSPERO (CRD420251018990).
BACKGROUND: Inflammation, nutritional status, and cardiovascular health are all correlated withmortality in cancer survivors, yet their combined effect remains unclear. RESEARCH DESIGN AND METHODS: We included 2,322 canc...BACKGROUND: Inflammation, nutritional status, and cardiovascular health are all correlated withmortality in cancer survivors, yet their combined effect remains unclear. RESEARCH DESIGN AND METHODS: We included 2,322 cancer survivors from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 cycles. The Advanced Lung Cancer Inflammation Index (ALI), reflecting inflammatory burden and nutritional status, and Life's Essential 8 (LE8), representing cardiovascular health, were categorized into tertiles and three-level groups, respectively. Survey-weighted multivariable Cox models estimated hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: In multiple adjusted models, higher ALI was correlated with lower all-cause mortality (HR 0.63; 95% CI 0.47-0.84) and non-cancer mortality (HR 0.55; 95% CI 0.39-0.77). Similarly, elevated LE8 scores were linked to reduced risks of all-cause (HR 0.56; 95% CI 0.33-0.95) and non-cancer mortality (HR 0.39; 95% CI 0.22-0.67). Furthermore, high ALI was correlated with the lowest risk of all-cause mortality (HR, 0.38; 95% CI, 0.17-0.87) and non-cancer mortality (HR, 0.19; 95% CI, 0.06-0.56) death among cancer survivors who were high LE8 score. CONCLUSIONS: High ALI and LE8 together reduce all-cause and non-cancer mortality in cancer survivors, supporting combined nutritional-inflammatory and cardiovascular optimization for longer survival.
INTRODUCTION: The tumor microbiome, a diverse microbial community within the tumor microenvironment (TME), significantly influences cancer progression and immunotherapy outcomes in colorectal cancer (CRC). Understanding...INTRODUCTION: The tumor microbiome, a diverse microbial community within the tumor microenvironment (TME), significantly influences cancer progression and immunotherapy outcomes in colorectal cancer (CRC). Understanding its role in modulating immune responses and therapeutic resistance is critical for advancing precision oncology. AREAS COVERED: This review examines the tumor microbiome's impact on CRC immunotherapy, focusing on immune checkpoint inhibitors (ICIs) like anti-PD-1/PD-L1 and anti-CTLA-4. It explores microbial composition, their immune-modulatory mechanisms, and metabolite-driven resistance pathways, including short-chain fatty acids and polyamines. Emerging strategies such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and targeted antibiotics are discussed, alongside challenges in personalizing microbiome-based therapies. Literature was sourced from peer-reviewed studies on tumor microbiome dynamics and immunotherapy resistance. EXPERT OPINION: The tumor microbiome shapes CRC immunotherapy efficacy by modulating immune evasion and TME dynamics. Targeted interventions like FMT and probiotics show promise in enhancing ICI responses, but challenges include microbial variability, safety concerns, and ethical considerations. Future research should prioritize personalized microbiome profiling and standardized protocols to optimize therapeutic outcomes and overcome resistance in CRC.
BACKGROUND: Mucinous adenocarcinoma of the appendix (MACA) has high metastatic potential and poor prognosis, lacking predictive models. This study aimed to establish models for assessing distant metastasis (DM) risk and...BACKGROUND: Mucinous adenocarcinoma of the appendix (MACA) has high metastatic potential and poor prognosis, lacking predictive models. This study aimed to establish models for assessing distant metastasis (DM) risk and survival prognosis of MACA patients with DM. RESEARCH DESIGN AND METHODS: SEER database data of MACA patients diagnosed from 2010 to 2021 were collected. Univariate and multivariate logistic regression identified DM risk factors, while Cox regression determined prognostic factors for DM patients. Two nomograms were created and evaluated via ROC curves, calibration curves, and DCA. Results: A total of 1722 patients with MACA were included, and 832 patients had DM at the time of diagnosis. The independent risk factors for DM in patients with MACA include gender, age, tumor size, T stage, and N stage. For MACA patients with DM, age, N stage, and surgical treatment were independent risk factors for overall survival (OS). The diagnostic and prognostic nomograms showed good discriminatory ability and calibration. The independent prognostic factors for MACA patients with DM are age, N stage, and surgery. CONCLUSIONS: The established diagnostic and prognostic models can quantitatively assess the risk and prognosis of MACA with DM, providing more effective guidance for clinical decision-making.
INTRODUCTION: Adipokines are bioactive signaling molecules secreted from adipose tissue (AT) that have regulatory functions in maintaining metabolic homeostasis. In physiological conditions, balanced adipokine secretion...INTRODUCTION: Adipokines are bioactive signaling molecules secreted from adipose tissue (AT) that have regulatory functions in maintaining metabolic homeostasis. In physiological conditions, balanced adipokine secretion supports metabolic stability and organ function. However, disruption of this balance can promote chronic inflammation and increase cancer risk. While their role in normal physiology is recognized, biological functions of adipokines in renal cell carcinoma (RCC) remain partially understood. AREAS COVERED: This review explores the biological functions of key adipokines such as adiponectin, leptin, visfatin, nesfatin-1, apelin, and omentin-1 in normal cellular processes and RCC. A search of the literature on PubMed, Web of Science, and Embase databases was performed from January 2000 through April 2025. This review summarizes findings on how these adipokines influence tumor biology, with a specific focus on their emerging roles in RCC. The review includes new findings and their possible limitations and the complexity of adipokine signaling and their roles in promoting or inhibiting tumorigenesis. EXPERT OPINION: The current evidence highlights adipokines as promising mediators in RCC biology; however, their mechanisms of action remain unclear. Further mechanistic studies are essential to unravel how adipokines regulate tumor initiation and progression. Without such understanding, the rational design of targeted therapies remains limited.
BACKGROUND: The prognosis for patients with advanced pancreatic cancer (PC) remains extremely poor, underscoring the critical need to explore and optimize systemic treatment strategies. This study aimed to evaluate the e...BACKGROUND: The prognosis for patients with advanced pancreatic cancer (PC) remains extremely poor, underscoring the critical need to explore and optimize systemic treatment strategies. This study aimed to evaluate the efficacy and safety of combining EGFR monoclonal antibodies (Anti-EGFR-mAb) with gemcitabine-based chemotherapy as a first-line treatment for locally advanced or metastatic PC. RESULTS: A total of 11 studies were included, with a total sample size of 806 patients with locally advanced or metastatic PC. Meta-analysis results showed that the objective response rate (ORR) for first-line treatment of advanced PC with Anti-EGFR-mAb combined with gemcitabine was 15% (95% CI: 10-22%), and the disease control rate (DCR) was 58% (95% CI: 49-67%). Compared with gemcitabine-based chemotherapy, combination therapy did not improve progression-free time (PFS) (HR = 0.93, 95%CI: 0.81-1.04, = 0.057) or overall survival (OS) (HR = 0.90, 95%CI: 0.78-1.02, = 0.04). The incidence of severe adverse events (sAEs) caused by combination therapy was 31% (95% CI: 14-50%). CONCLUSIONS: Anti-EGFR-mAb combined with gemcitabine chemotherapy has shown a good efficacy to first-line treatment of advanced PC, it did not provide a significant survival benefit compared to chemotherapy alone. Additionally, combination therapy was associated with a high incidence of AEs, highlighting safety concerns that warrant special attention. REGISTRATION: PROSPERO (CRD420250652874).
INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of solid tumors. This meta-analysis of randomized controlled trials aimed to assess the survival benefit of anti-PD-1/PD-L1 therapies in...INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of solid tumors. This meta-analysis of randomized controlled trials aimed to assess the survival benefit of anti-PD-1/PD-L1 therapies in women with advanced or recurrent endometrial cancer (EC) and mismatch repair deficiency (dMMR). METHODS: A systematic search was conducted in PubMed, Scopus, Cochrane, and Web of Science databases to compare PD-1/PD-L1 inhibitors versus standard therapy in patients with advanced/recurrent EC. Studies were screened based on predefined inclusion/exclusion criteria. Risk of bias was assessed using the Cochrane Risk of Bias Tool. We used DerSimonian and Laird random-effects models to estimate hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Five studies including 2,739 patients were analyzed, with 627 (22.90%) having dMMR tumors. ICIs significantly improved progression-free survival (HR 0.35; 95% CI 0.28-0.44) and overall survival (HR 0.40; 95% CI 0.28-0.57) in dMMR patients. No significant difference was found in objective response rate (RR 1.72; 95% CI 0.88-3.36). CONCLUSIONS: The addition of immunotherapy for treating patients with advanced or recurrent endometrial cancer with dMMR and high microsatellite instability significantly improved PFS and OS outcomes. REGISTRATION: PROSPERO (CRD22057890200).
INTRODUCTION: Genomic profiling has revolutionized the management of Urothelial carcinomas (UC), particularly in muscle-invasive bladder cancer (MIBC) and metastatic UC, by identifying molecular subtypes and actionable m...INTRODUCTION: Genomic profiling has revolutionized the management of Urothelial carcinomas (UC), particularly in muscle-invasive bladder cancer (MIBC) and metastatic UC, by identifying molecular subtypes and actionable mutations that guide personalized therapies and prognostication. AREAS COVERED: The integration of genomic profiling in UC, potential prognostic and predictive biomarkers of prognosis, and the current landscape of systemic therapies in UC, including FGFR inhibitors (FGFRi), antibody-drug conjugates (ADC), immune checkpoint inhibitors (ICI), and chemotherapy are discussed herein as a narrative and descriptive review. EXPERT OPINION: Genomic profiling has advanced our understanding of UC diagnosis and treatment, but its routine clinical use remains limited to confirming biomarkers such as FGFR alterations and HER2 amplification for approved targeted therapies such as erdafitinib, a FGFRi, and trastuzumab deruxtecan, a HER2-directed ADC. Testing for other biomarkers such as PD-L1, tumor mutational burden (TMB), and Nectin-4 can be useful, but not required for the use of ICI and enfortumab vedotin. Circulating tumor DNA (ctDNA) is an emerging tool for monitoring disease and guiding therapy, with trials underway to confirm its clinical utility.