Background:Melanoma treatment encompasses surgery, chemotherapy, radiotherapy, immunotherapy, and targeted therapy. Despite declining mortality due to therapeutic advances, increasing incidence underscores the growing importance of cost-effectiveness analyses. The integration of cost-effectiveness evaluation with Bayesian meta-analysis and meta-regression may enhance the synthesis of heterogeneous evidence. Methods:A systematic literature review was conducted to identify studies reporting quality-adjusted life years (QALYs) and direct treatment costs for melanoma in PubMed, MEDLINE, and MEDLINE Ultimate. Bayesian meta-analysis with non-informative priors was applied to derive pooled estimates and quantify uncertainty. Results:A total of 272 studies were identified, of which only a limited subset met the inclusion criteria. The studies exhibited substantial heterogeneity in treatments, populations, time horizons, perspectives, and costs. Meta-analysis based on the effects provided in one study showed that chemotherapy demonstrated lower effectiveness, as measured by QALYs, compared with treatment sequences such as Anti-PD1 → Bi-TT and Bi-TT → Anti-PD1 in both BRAF-mutated and wild-type populations. Lower costs were associated with chemotherapy, ipilimumab, and Anti-PD1 relative to combination and sequential regimens. Meta-analysis based on the effects provided in another study showed that treatment costs increased with advancing disease stage (≥IIIA) and exhibited greater variability in advanced melanoma. Conclusion:The combined methodological approach enhances the robustness and comparability of estimates. The observed variability in both clinical effectiveness and costs, across treatment strategies and disease stages, has important implications for healthcare decision-making and resource allocation.
Background and Purpose:The multicenter precision oncology registry INFINITY investigated biomarker-driven therapy and outcomes in patients with advanced malignancies not eligible for standard therapy in routine clinical care in Germany. Although programmed cell death (ligand) 1 (PD-(L)1) antibodies have changed the treatment landscape of several malignancies and PD-(L)1 expression level is predictive and therefore often used for treatment selection, existing predictive biomarkers are insufficient to identify patients who will benefit from PD-(L)1 inhibitor-based therapy. This project aimed to identify genomic tumor profiles predicting benefit from anti-PD-(L)1 therapy. Patients and Methods:Patients from the INFINITY registry treated with anti-PD-(L)1 monotherapy were stratified into two cohorts using a case-control design: clinical benefit (treatment duration >182 days) and no clinical benefit (treatment duration 22-63 days). Tumor tissue samples from the virtual biobank were requested from local pathologies and sent to the central pathology for next‑generation sequencing (NGS) using the OncomineTM Comprehensive Assay Plus panel (Thermo Fisher, NGS pan-cancer assay). Results:Of the 26 patients with clinical benefit and 24 patients without clinical benefit, NGS-based genetic tumor profiles were available for 11 and 8 patients, respectively. Only patients with clinical benefit from anti-PD-(L)1 therapy showed genetic alterations in KEAP1, PIK3CA and MRE11. Conclusion:Our analysis revealed a set of three genes (KEAP1, PIK3CA and MRE11) exclusively mutated in patients with clinical benefit from PD-(L)1-inhibitor therapy, possibly representing promising biomarker candidates. Given the small sample size and the heterogeneous tumor types included, these findings are exploratory, and validation in larger, preferably tumor-type-specific cohorts is required before any predictive value can be attributed to these genomic alterations.
Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of hematological malignancies, whose diagnosis is often delayed and requires highly individualized therapeutic strategies. We report an unusual case of a highly probable r/r MF/SS in a 66-year-old male initially diagnosed with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), based on an atypical leukemic presentation without skin involvement. Cutaneous lesions developed during the disease course, prompting then for a retrospective diagnostic reassessment. Expression of KIR3DL2 on circulating malignant cells, along with a clonal TCR-gamma rearrangement present in both the blood and the skin, and a TP53 nonsense variant, led to a revision of the diagnosis to mycosis fungoides (MF) and Sézary syndrome (SS). MF/SS are the most prevalent CTCL subtypes and are associated with a poor prognosis in advanced stages, largely due to the lack of effective treatments that can achieve sustained remission. Therapeutic options for patients with relapsed/refractory (r/r) MF/SS remain limited and long-term disease control is uncommon. After failure of two treatment lines, including CHOEP-based chemotherapy and bendamustine-brentuximab vedotin (B-BV), the patient received belinostat, a histone deacetylase inhibitor (HDACi). Following three cycles of belinostat, complete cutaneous remission and a partial hematological response were achieved and have been maintained for more than six years (79 cycles to date). Treatment was well tolerated, with only mild anemia. This case highlights the potential role of belinostat in the management of advanced MF/SS and suggests that durable disease control may be achievable in selected r/r patients. Further investigations are warranted to better identify the patients most likely to benefit from belinostat therapy.
Background:This study aimed to evaluate the therapeutic efficacy and safety profile of pembrolizumab in patients with recurrent and advanced cervical cancer. Methods:A systematic literature search was conducted in six databases, including Web of Science, PubMed, Embase, Scopus, Cochrane Library, and Google Scholar, from database inception to March 2026. Studies evaluating pembrolizumab monotherapy or pembrolizumab-containing combination therapy in patients with recurrent or advanced cervical cancer were included. Pooled analyses were performed to estimate survival outcomes, tumor response rates, and adverse events using fixed-effects or random-effects models according to the degree of heterogeneity. Subgroup analyses were conducted according to study design and treatment strategy. Results:Eleven studies involving 1`111 patients with recurrent or advanced cervical cancer were included in the meta-analysis. Pooled median overall survival (mOS) was 10.82 months (95% CI:8.89-12.76), and the pooled median progression-free survival (mPFS) was 3.47 months (95% CI:2.61-4.34). The pooled overall response rate was 0.30 (95% CI:0.16-0.49), while pooled disease control rate was 0.57 (95% CI:0.36-0.76). Subgroup analyses showed that combination therapy significantly improved the mPFS and tumor response outcomes compared to monotherapy. Clinical trials have demonstrated higher response rates than retrospective studies. Pooled survival outcomes improved in PD-L1-positive patients. Regarding safety, the most common any-grade adverse events included anemia, fatigue, diarrhea, nausea, and vomiting, whereas grade 3-5 adverse events occurred at relatively low frequencies. Conclusion:Pembrolizumab demonstrated promising efficacy and a manageable safety profile in patients with recurrent or advanced cervical cancer. Combination therapy appears to provide superior clinical benefits compared with monotherapy. Further large-scale prospective studies are warranted to confirm these findings and better identify patient subgroups that may derive the greatest benefit from pembrolizumab-based therapy.
Background:(m)FOLFOXIRI plus bevacizumab has improved outcomes in selected patients with metastatic colorectal cancer (mCRC), but data from Southeast Asia remain limited. This study evaluated survival outcomes and factors associated with progression-free survival (PFS) and overall survival (OS) among Vietnamese patients with mCRC receiving first-line mFOLFOXIRI plus bevacizumab. Methods:In this retrospective real-world cohort study, 76 patients with mCRC treated with first-line mFOLFOXIRI plus bevacizumab were included. Tumor response, early tumor shrinkage (ETS), depth of response (DpR), PFS and OS were assessed. Survival outcomes were estimated using the Kaplan-Meier method, and exploratory prognostic factors were analyzed using Cox proportional hazards models. Results:A total of 76 patients were included, with a median age of 59.5 years; 61.8% were male, 65.8% had left-sided tumors, and 46.1% had metastases in ≥2 organs. The objective response rate (ORR) was 73.7%, and the disease control rate (DCR) was 97.4%. ETS was achieved in 56.6% of patients, with a median DpR of 40.0%. Molecular profiling showed RAS mutations in 49.3%, BRAF V600E in 5.5%, and PIK3CA mutations in 9.6%. Median PFS was 14.9 months (95% CI, 10.3-19.4), and median OS was 27.0 months (95% CI, 12.4-41.7), with 12- and 24-month OS rates of 81.8% and 56.3%, respectively. In multivariable analysis, ETS remained independently associated with improved PFS (HR 0.36, 95% CI 0.19-0.67; P = 0.001) and OS (HR 0.25, 95% CI 0.11-0.61; P = 0.002). High tumor burden (≥2 metastatic organs) was independently associated with shorter PFS, while elevated baseline CA19-9 was independently associated with inferior OS. Conclusion:In this Vietnamese retrospective real-world cohort, first-line mFOLFOXIRI plus bevacizumab achieved clinically meaningful response and survival outcomes. ETS was independently associated with improved survival and may serve as a useful prognostic indicator.
SnoRNAs are regulatory RNAs that play indispensable roles in ribosomal RNA processing and translation. Their distinct structural conformations determine specific protein-binding partners, thereby mediating diverse epigenetic modifications. Most snoRNAs are transcribed from introns of snoRNA host genes (SNHGs). Processed snoRNAs can further yield piwi-interacting RNAs (piRNAs) and snoRNA-derived fragments (sdRNAs). These small RNA products are frequently dysregulated in tumors and exert significant oncogenic functions. In cancer, snoRNA dysregulation stems from DNA-level alterations such as chromosomal aberrations, base mutations, and gene silencing, as well as RNA-level disruptions including aberrant post-transcriptional modifications, degradation, and trafficking. Such dysregulated snoRNAs drive malignant hallmarks-sustained proliferation, invasion and metastasis, angiogenesis, metabolic reprogramming, immune evasion, senescence bypass, epigenetic remodeling, phenotypic plasticity, and microbiome-host crosstalk-through mechanisms spanning histone modifications, nucleic acid epitranscriptomics, and competitive endogenous RNA (ceRNA) networks. Consequently, tumor-associated snoRNAs detectable in body fluids represent promising non-invasive biomarkers for early cancer diagnosis and prognosis prediction. This review systematically summarizes snoRNA biogenesis pathways, elucidates mechanisms underlying their dysregulation in malignancies, summarizes the impact of aberrant snoRNAs on tumorigenesis and progression, and highlights clinically significant snoRNAs for diagnostic and therapeutic applications.
Immune checkpoint inhibitors (ICIs) can induce a spectrum of immune-related adverse events (irAEs), yet sequential, multi-organ severe irAEs remain uncommon and challenging to manage. We present a 78-year-old male patient with esophageal squamous cell carcinoma, suspected to have developed continuous, life-threatening irAEs involving the liver, bone marrow, and lungs after receiving sintilimab combined with chemotherapy. All events were successfully controlled through glucocorticoid treatment and multidisciplinary collaboration support. However, it should be noted that during the tapering of steroids, existing irAE symptoms may worsen or new adverse reactions may occur. This case emphasizes that sintilimab may trigger a severe, sequential multi-system irAEs, potentially suggesting a progressive breakdown of immune tolerance, though direct evidence is lacking. It highlights the critical need for prolonged, vigilant multi-organ monitoring in elderly patients receiving ICIs, especially in combination regimens, and suggests that sustained immunomodulation may be required to control subsequent irAEs even after initial toxicity resolution.
Introduction: Elongase of very long-chain fatty acids 6 (ELOVL6), a key enzyme in long-chain fatty acid elongation, has been implicated in tumour progression, but its role in oral squamous cell carcinoma (OSCC) remains unclear. Methods: In vitro experiments were performed using OSCC cell lines with ELOVL6 knockdown or over-expression and assessed with CCK-8, scratch, transwell migration and invasion assays, lipidomic profiling, immunofluorescence, and quantitative PCR. Results: ELOVL6 knockdown (KD-ELOVL6) significantly reduced cell proliferation, migration, and invasion, whereas ELOVL6 over-expression (OE-ELOVL6) enhanced these malignant phenotypes. Lipidomic analysis revealed decreased palmitic acid and increased oleic acid and other long-chain fatty acids in OE-ELOVL6 cells. Similarly, fatty acid metabolism-related genes (ACS, ACC, SCD1, and FAS) were upregulated. No significant changes in the expression of endoplasmic reticulum (ER) stress markers were observed. Immunofluorescence staining demonstrated that ELOVL6 expression was positively correlated with intracellular ROS levels. Conclusion: ELOVL6 may modulate ROS levels and fatty acid metabolism rather than the endoplasmic reticulum stress, thereby affecting the proliferation and migration of OSCC cells in vitro.
Primary hepatic epithelioid gastrointestinal stromal tumor (GIST) is an extremely rare neoplasm. Due to its non‑specific clinical and radiologic features, it is frequently misdiagnosed as other primary or metastatic hepatic malignancies. Here, we report the case of an 85‑year‑old asymptomatic woman in whom a mass in the left hepatic lobe was incidentally identified during routine examination. Computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography‑CT revealed a well‑defined malignant lesion in the left hepatic lobe without evidence of extrahepatic disease. The patient underwent neoadjuvant transarterial chemoembolization (TACE), followed by left hemihepatectomy one month later. Histopathologic and immunohistochemical analyses confirmed a high‑risk epithelioid GIST. Adjuvant therapy with oral imatinib (400 mg/day) was initiated six weeks postoperatively. At the 10‑month follow‑up, the patient remained free of tumor recurrence. Despite preoperative diagnostic challenges, the combination of neoadjuvant TACE, curative surgical resection, and adjuvant imatinib resulted in favorable short‑term outcomes in this patient.
Background: As the core treatment for cervical cancer, chemoradiotherapy efficacy is often limited by tumor heterogeneity-driven resistance. During chemoradiotherapy, the tumor microenvironment undergoes dynamic remodeling, with residual malignant cells evolving adaptively. However, the key regulatory genes driving therapeutic resistance remain elusive at single-cell resolution, which hinders the development of novel targeted therapies. Methods: Single-cell RNA sequencing (scRNA-seq) was performed on paired clinical samples from three cervical cancer patients before and after chemoradiotherapy to identify the cellular changes and the molecular mechanisms induced by chemoradiotherapy. Through integrated multi-omics data analysis, non-heterogeneity-dependent genes with prognostic value were identified. Furthermore, the biological function of the candidate gene in chemoradiotherapy-resistant HeLa cells was verified through in vitro functional experiments, including the detection of cell proliferation, migration and invasion abilities. Results: Chemoradiotherapy significantly reprogrammed the cellular composition of the tumor microenvironment (TME) in cervical cancer. Residual malignant cells showed activation of angiogenesis, epithelial-mesenchymal transition, stress-response, and cell-cycle programs. Eight heterogeneity-filtered prognostic genes were identified, and phosphoglucomutase 2 (PGM2) was prioritized because it was upregulated in cervical cancer, enriched in malignant cells, associated with poor prognosis, and supported by independent transcriptomic, spatial, and immunohistochemical evidence. PGM2 knockdown reduced proliferation, migration, and invasion in resistant HeLa cells. Conclusion: PGM2 may contribute to the malignant phenotype of chemoradiotherapy-resistant cervical cancer cells and represents a candidate biomarker and therapeutic target. Further validation in larger clinical cohorts and laboratory work is needed before clinical translation.
Immunotherapy in colorectal cancer (CRC) presents a striking dichotomy. MSS/pMMR tumors account for approximately 95% of metastatic CRC cases, representing a substantial global health burden. While immune checkpoint inhibitors (ICIs) have revolutionized treatment for mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic CRC-achieving durable responses in tumors with high mutational burden and a T-cell-inflamed microenvironment-the majority of microsatellite stable (MSS) cases remain resistant. The MSS tumor microenvironment is typically "cold", featuring low neoantigen load, poor T-cell infiltration, and dominant immunosuppressive networks. To overcome this resistance, extensive research is focused on combination strategies (ICIs with anti-angiogenic agents, targeted therapies, chemotherapy, radiotherapy) and next-generation modalities (adoptive cell therapies, bispecific antibodies, cancer vaccines). This review examines the biological basis for this dichotomy, summarizes clinical evidence in dMMR/MSI-H CRC, and critically assesses emerging strategies for MSS disease. We propose that future progress will likely depend on mechanism-based, biomarker-driven approaches that match specific immune evasion patterns with rationally designed interventions, with the goal of extending immunotherapy benefits to broader CRC populations. This narrative review synthesizes peer-reviewed literature from PubMed and clinical trial registries (2015-2025), prioritizing Phase II/III trials and mechanistic studies.
Bacillus Calmette Guerin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC) remains a difficult clinical setting in which radical cystectomy offers the most reliable oncologic control but is not feasible or acceptable for many patients. This review examines contemporary bladder-preserving strategies, with emphasis on biologic intravesical platforms, device-assisted drug-delivery systems, systemic immunotherapy, and pragmatic intravesical chemotherapy alternatives. These approaches should not be viewed as interchangeable. Biologic platforms seek to restore or intensify local antitumor immunity, whereas device-assisted strategies aim to overcome the pharmacokinetic limitations of conventional intravesical therapy by improving residence time, exposure, or tissue penetration. Across platforms, clinically meaningful activity has been reported, but current evidence remains constrained by single-arm study designs, heterogeneous eligibility criteria, non-equivalent endpoints, and variable follow-up maturity. As a result, available data support expansion of bladder-preserving options but do not establish a definitive treatment hierarchy. In clinical practice, differences in durability, toxicity, treatment burden, BCG dependence, device requirements, access, and biomarker eligibility may be as important as initial response rates. The central challenge is therefore shifting from whether bladder preservation is possible to how available options should be selected, sequenced, and integrated for individual patients. More harmonized comparative evidence, mature post-failure data, and clinically deployable biomarker frameworks will be needed to guide future treatment allocation.
