Gao X, Gao S, Yang Y
… +4 more, Xing D, Mao Z, Ren Y, Chen J
J Cancer Res Clin Oncol
· 2026 Jan · PMID 41563498
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BACKGROUND: Gastric cancer (GC) is one of the most prevalent and aggressive malignancies globally, characterized by high morbidity and mortality rates despite advancements in medical technologies and screening methods. R...BACKGROUND: Gastric cancer (GC) is one of the most prevalent and aggressive malignancies globally, characterized by high morbidity and mortality rates despite advancements in medical technologies and screening methods. Recent studies have suggested that long non-coding RNAs (lncRNAs), particularly aspartyl-tRNA synthetase antisense RNA 1 (DARS-AS1), may play significant roles in tumor progression; however, its specific function in GC remains unclear. Therefore, this study aimed to clarify the contribution of DARS-AS1 to the progression and prognosis of GC. METHODS: We utilized quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) to assess DARS-AS1 and CD31 expression levels in GC tissues derived from various cohorts. Additionally, functional studies involving knockdown of DARS-AS1 in GC cells were conducted to evaluate the effects on migration and angiogenesis in human umbilical vein endothelial cells (HUVECs) mediated by exosomes. RESULTS: Our analyses revealed that DARS-AS1 is significantly upregulated in GC tissues and is associated with malignant progression and poor prognosis. Furthermore, elevated DARS-AS1 levels correlated positively with tumor microvessel density (MVD). The knockdown of DARS-AS1 resulted in decreased migration and tube-forming ability of HUVECs in vitro. Mechanistically, we demonstrated that the exosomal transfer of DARS-AS1 from GC cells activates the Wnt/β-catenin signaling pathway by targeting miR-605-5p, thus promoting angiogenesis. CONCLUSION: Our findings highlight the pivotal role of DARS-AS1 in enhancing GC progression through the activation of angiogenesis via the Wnt signaling pathway. By elucidating the mechanism underlying DARS-AS1-mediated tumorigenesis, we posit that DARS-AS1 could serve as a prognostic biomarker and a potential therapeutic target for GC intervention, warranting further exploration in clinical settings.
Bielack SS, Andreou D, Baumhoer D
… +14 more, Blattmann C, Friedel G, Fröhlich B, Harrabi SB, Kager L, von Kalle T, Kessler T, Kevric M, Knoll A, Kühne T, Reichardt P, Sorg B, Windhager R, Hecker-Nolting S
J Cancer Res Clin Oncol
· 2026 Jan · PMID 41559504
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PURPOSE: To describe Undifferentiated Pleomorphic Sarcoma of Bone (UPSB) treated in Germany, Austria, or Switzerland and using the same treatment-approach as for osteosarcoma. PATIENTS AND METHODS: The database of the Co...PURPOSE: To describe Undifferentiated Pleomorphic Sarcoma of Bone (UPSB) treated in Germany, Austria, or Switzerland and using the same treatment-approach as for osteosarcoma. PATIENTS AND METHODS: The database of the Cooperative Osteosarcoma Study Group (COSS) was screened for UPSB. Eligible patients were evaluated for patient, tumor, and treatment related variables, and outcomes. RESULTS: One-hundred thirty-two eligible patients were identified (median age 41.7 (range: 10.3-74.6) years; males 58%; preceding malignancies 11%; tumor-sites extremities 86%, trunk 12%, head & neck 2%). Relative tumor size was < 1/3 of the involved bone in 83% of evaluable cases, pathologic fractures were present in 14% (limb-primaries only), and primary distant metastases in 6%. All patients received chemotherapy and 96% surgery for their primary (81% limb-salvage for extremity lesions). The response rate to preoperative chemotherapy was 38%. After a median follow-up of 3.9 (1 day-34.1) years for event-free and 5.2 (0.2-34.1) years for overall survival, the 5 year event-free and overall survival probabilities were 63% (standard error: 5%) and 70% (4%), respectively. Younger patient age, an extremity tumor, and localized disease predicted superior outcomes, pathologic fractures and limb-salvage surgery worse. The extent of tumor response to pre-operative chemotherapy seemed to have no impact on prognosis. DISCUSSION: UPSB generally affects considerably older persons than does the more frequent osteosarcoma. Despite a lower response rate to preoperative chemotherapy, its prognosis is at least comparable, if not better. Several prognostic factors impacting outcome could be defined. These results provide a benchmark for this rare disease.
J Cancer Res Clin Oncol
· 2026 Jan · PMID 41559233
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INTRODUCTION:BCR::ABL1-negative myeloproliferative neoplasms are chronic diseases characterized by high symptom burden due to systemic inflammation. Treatment objectives include cytoreduction and alleviation of symptoms...INTRODUCTION:BCR::ABL1-negative myeloproliferative neoplasms are chronic diseases characterized by high symptom burden due to systemic inflammation. Treatment objectives include cytoreduction and alleviation of symptoms. Besides standard therapies, complementary and alternative medicine (CAM) methods are frequently used and requested by cancer patients. Aim of this study was to assess the interest in and use of CAM by patients diagnosed with MPN. METHODS: This study was conducted as a patient-reported, paper-and-pencil-based questionnaire. RESULTS: 166 patients with MPN were included, 72 (43.4%) male and 94 (56.6%) female. Median age was 65.0 years. Diagnoses included ET 66/166 (39.8%), PV 40/166 (24.1%), MF 51/166 (30.7%) MPN-U 8/166 (4.8%) and SM-AHN 1/166 (0.6%). Overall, more frequent use of CAM was documented in females (59.6%) compared to males (41.7%), p = 0.022. A significant proportion of patients reported on the ingestion of nutritional supplements: 44/163 (26.5%) vitamin D, 26/165 (15.7%) vitamin C, 19/165 (11.4%) zinc, 13/165 (7.8%) secondary plant products, 12/165 (7.2%) selenium, and 19/165 (11.4%) multivitamin preparations. Regarding other CAM-related measures: 5/164 (3.0%) used amygdalin, 4/164 (2.4%) mistletoe therapy, 11/165 (6.6%) acupuncture, 6/165 (3.6%) homeopathy, 11/165 (6.6%) yoga, 10/165 (6%) reported receiving spiritual support, while 3/165 (1.8%) used the services of "healers". A higher rate of CAM use was found among patients with longer disease duration. CONCLUSIONS: Use of CAM was recorded in the majority of patients with MPN. Higher use of CAM-related measures was reported by women and patients with longer disease duration. Patients should be regularly consulted about the use of CAM, its risks should be considered and pointed out, and safe methods should be recommended.
J Cancer Res Clin Oncol
· 2026 Jan · PMID 41530333
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PURPOSE: Beyond standardized screenings, clinical assessments by psycho-oncologists during initial consultations play a key role in guiding psychosocial cancer care. Despite their relevance, these assessments have rarely...PURPOSE: Beyond standardized screenings, clinical assessments by psycho-oncologists during initial consultations play a key role in guiding psychosocial cancer care. Despite their relevance, these assessments have rarely been systematically examined. The aim of this study was to analyze psycho-oncologists' assessments of psychological distress and support needs and to identify factors influencing their assessments. METHODS: In a cross-sectional study, N = 9 psycho-oncologists retrospectively evaluated N = 1048 initial psychooncological consultations. The perceived psychological distress, depression, anxiety, health literacy and support needs of patients were recorded, as well as consultation-related conditions and the psycho-oncologists' own stress levels. Analyses involved descriptive statistics, group comparisons, correlations, and a binomial logistic regression. RESULTS: A distress score ≥ 5 was observed by psychooncologists in 74.7% of patients; 44.5% were rated as anxious, 28.6% as depressed. Mental health diagnoses were made in 25% of cases, mainly adjustment or affective disorders. Psycho-oncological support needs were identified in 75.6% of patients. Key predictors for identifying distress and needs included patients' desire for support (OR = 45.06), Knowledge and information about the consultation (OR = 2.66), and psycho-oncologists' own stress levels (OR = 1.53). CONCLUSION: Psycho-oncological initial assessments are clinically relevant, but are subject to contextual and personal influences. The structured collection of consultation requests, information awareness, and health literacy, as well as interdisciplinary collaboration, can improve the assessment. The psychological stress of psycho-oncologists should also be systematically taken into account.
J Cancer Res Clin Oncol
· 2026 Jan · PMID 41511559
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Leptomeningeal metastasis in patients with Epidermal Growth Factor Receptor-mutant non-small cell lung cancer carries a dismal prognosis and is associated with profound neurological morbidity. Historically, therapeutic e...Leptomeningeal metastasis in patients with Epidermal Growth Factor Receptor-mutant non-small cell lung cancer carries a dismal prognosis and is associated with profound neurological morbidity. Historically, therapeutic efficacy has been severely limited, leading to poor overall survival. This review aims to synthesize the recent, albeit incremental, advances in the multidisciplinary management of this devastating complication. We delve into the evolving landscape of treatment modalities, with a particular focus on the latest generation of tyrosine kinase inhibitors and their superior central nervous system penetration. The roles of conventional approaches, including radiotherapy (both whole-brain and focal) for symptom palliation and tumor control, and intrathecal chemotherapy, are critically re-evaluated in the modern context. Furthermore, we explore the rationale and early evidence for novel combination strategies. A significant portion of our analysis is dedicated to evaluating the pharmacodynamic mechanisms of action, optimizing dosing strategies, and interpreting clinical outcomes from key trials and real-world evidence. Central to the discussion are the persistent challenges of adequate blood-brain barrier penetration, the emergence of therapeutic resistance, and the management of overlapping toxicities. We also address the parallel progress in diagnostic neuro-imaging and cerebrospinal fluid liquid biopsies, which are enhancing early detection and disease monitoring. Finally, this review outlines future research directions, emphasizing the need for randomized controlled trials and a deeper understanding of the tumor microenvironment to foster a paradigm shift in the care of patients with leptomeningeal metastasis.
J Cancer Res Clin Oncol
· 2026 Jan · PMID 41507508
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BACKGROUND: Acupuncture is a method of traditional Chinese medicine that has been adapted in the Western world. The objective of this study was to critically assess the evidence presented in randomized controlled trials...BACKGROUND: Acupuncture is a method of traditional Chinese medicine that has been adapted in the Western world. The objective of this study was to critically assess the evidence presented in randomized controlled trials (RCTs) about the effectiveness of acupuncture on fatigue in cancer patients. METHOD: In April 2024 a systematic search was conducted searching five electronic databases to find studies concerning the use, effectiveness and potential harm of acupuncture therapy on cancer patients. RESULTS: From all (1599) search results, 15 studies with 1346 patients were included. Acupuncture methods varied (e.g., traditional-, electro-, mind-regulating and ATAS-acupuncture) and were compared to sham acupuncture, usual care, or other controls. Studies comparing acupuncture to sham acupuncture reported mixed results: while some found significant effects on cancer-related fatigue, others found no advantages. Studies comparing acupuncture to usual care or waitlist controls often reported positive effects. However, the reliability of these findings is limited, as 14 of 15 studies were rated as "high risk of bias" by the RoB-2 tool due to issues like insufficient blinding and incomplete data analysis. Only one study, with low risk of bias, showed a significant reduction in fatigue with acupuncture compared to sham acupuncture (p < 0.001). GRADE evaluation also showed very low certainty of evidence. CONCLUSION: The heterogenous results and methodological limitations of the existing studies prevent us from drawing definitive conclusions about the effectiveness of acupuncture in the treatment of cancer-related fatigue. Despite the inclusion of 15 studies, the overall evidence remains insufficient due to widespread problems in study design and inconsistent results. This analysis highlights the need to use more rigorous designs and more comprehensive assessment tools in future studies to better understand the role of acupuncture in the management of fatigue after cancer treatment.
Abdulrazzak M, Björkhem-Bergman L, Villard C
… +3 more, Gerling M, Gustavell T, Jansson H
J Cancer Res Clin Oncol
· 2026 Jan · PMID 41504962
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BACKGROUND: Albumin in combination with other inflammatory markers has shown prognostic value in malignancy, including biliary tract cancer (BTC). This study aimed to evaluate the prognostic value of hypoalbuminemia alon...BACKGROUND: Albumin in combination with other inflammatory markers has shown prognostic value in malignancy, including biliary tract cancer (BTC). This study aimed to evaluate the prognostic value of hypoalbuminemia alone in patients with BTC, with stratified analyses according to tumor type, treatment and sex. METHODS: A retrospective regional referral center cohort study was conducted, including consecutive patients with a measurement of preoperative albumin and intended resection of suspected BTC: intrahepatic cholangiocarcinoma (iCCA), perihilar cholangiocarcinoma (pCCA) or gallbladder cancer (GBC) between 2009 and 2017. The primary outcome was overall survival (OS), analyzed by Kaplan-Meier estimate and Cox regression. RESULTS: Out of 221 patients, 191 underwent resection, while 30 patients were diagnosed with unresectable BTC (14%). In the resection group, 147 patients had confirmed BTC, while 44 (20%) were postoperatively diagnosed with a benign lesion. Hypoalbuminemia (< 35 g/L) was more frequent in pCCA (75%) and GBC (59%), compared to iCCA (34%, p < 0.001). The preoperative albumin level was positively associated with resectability (p = 0.025). In patients with resection, hypoalbuminemia was associated with a tumor positive resection margin (p < 0.001). Hypoalbuminemia was a negative prognostic factor in resectable (p < 0.001) and unresectable BTC (p < 0.001), and in both women (p = 0.002) and men (p = 0.004). Hypoalbuminemia was negatively associated with OS in iCCA (p < 0.001) and GBC (p = 0.022), but not in pCCA (p = 0.210). CONCLUSION: Preoperative albumin was prognostic for survival in patients with iCCA and GBC, in both women and men and regardless of tumor resectability. Patients with pCCA more often had low albumin, and hypoalbuminemia alone was not prognostic in this subgroup.
Hoberger M, Zuber RL, Burkhard-Meier A
… +13 more, Di Gioia D, Jurinovic V, Völkl M, Güler SE, Albertsmeier M, Klein A, Dürr HR, Schmidt-Hegemann NS, Knösel T, Kunz WG, von Bergwelt-Baildon M, Lindner LH, Berclaz LM
J Cancer Res Clin Oncol
· 2026 Jan · PMID 41504936
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PURPOSE: High-dose ifosfamide (HD-IFO) remains an effective regimen for advanced bone and soft tissue sarcomas, but predictors of long-term benefit are poorly defined. This study evaluated clinical outcomes and prognosti...PURPOSE: High-dose ifosfamide (HD-IFO) remains an effective regimen for advanced bone and soft tissue sarcomas, but predictors of long-term benefit are poorly defined. This study evaluated clinical outcomes and prognostic factors using machine learning-assisted modeling in sarcoma patients treated with HD-IFO at a high-volume academic center. METHODS: We retrospectively analyzed 26 patients with histologically confirmed bone or soft tissue sarcoma who received HD-IFO (≥ 12 g/m per cycle) between 2015 and 2025. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared across RECIST response categories using log-rank testing. Prognostic factors were identified using Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression with leave-one-out cross-validation. The top three variables were entered into multivariable logistic regression to estimate odds ratios (ORs) for OS > 24 months. RESULTS: Median PFS and OS from start of HD-IFO was 6.6 months (95% CI 4.4-9.8) and 24.7 months (95% CI, 14.7-34.2), respectively. Patients with progressive disease (PD) had significantly shorter OS than those with partial response (PR; p = 0.0047) or stable disease (SD; p = 0.0485). LASSO identified intervention prior to progression, prior tumor control ≥ 12 months, and absence of metastases as the strongest predictors for OS > 24 months. In multivariable analysis, intervention prior to progression (OR 24.18, 95% CI 1.81-1001.27, p = 0.037) and prior tumor control ≥ 12 months (OR 25.39, 95% CI 2.1-1008.9, p = 0.030) independently predicted OS > 24 months. CONCLUSION: HD-IFO provides durable disease control in selected sarcoma patients, particularly those with sustained prior tumor control and intervention prior to progression.
Liu Y, Wang F, Wang P
… +6 more, Zhou Z, Wang H, Li J, Qiu Y, Wang H, Miao S
J Cancer Res Clin Oncol
· 2026 Jan · PMID 41504919
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PURPOSE: Multidisciplinary team (MDT) consultations are crucial for managing pulmonary nodules, yet face challenges in efficiency, evidence-based decision support, and data utilization within the MDT process. We present...PURPOSE: Multidisciplinary team (MDT) consultations are crucial for managing pulmonary nodules, yet face challenges in efficiency, evidence-based decision support, and data utilization within the MDT process. We present an integrated artificial intelligence (AI)-MDT platform that serves as an assistive tool for lung cancer MDT workflows by incorporating AI across various processes.The aim of this study is to evaluate the clinical utility and preliminary efficacy of the AI-MDT platform. METHODS: The platform comprises three core modules: process automation, intelligent decision support, and diagnostic assistance. It integrates a real-time, evidence-based knowledge base powered by large language models and deep learning, with computer vision for automatic lesion detection and feature analysis. A web-based interface allows users to interact seamlessly with the AI-MDT platform. RESULTS: Since its implementation in November 2023 at a tertiary Grade A hospital in China, the platform has been involved in 879 consultations, including 811 patients. AI-generated diagnostic recommendations were utilized 852 times, and decision-making support was used in 744 cases. The platform significantly increased consultation volume, reduced expert time, and enhanced data utilization compared to traditional MDT. CONCLUSIONS: It offers clinicians tools to improve diagnostic quality and work efficiency, highlighting its significant clinical application value. These findings suggest that the proposed platform contributes to the emerging research on advances precision lung cancer management by integrating a continually updated evidence base and intelligent imaging methodologies, having potential implications for MDT processes across various medical specialties.
Chen X, Liu S, Li P
… +5 more, Luo L, Lin L, Jiang Q, Yu D, Tao R
J Cancer Res Clin Oncol
· 2026 Jan · PMID 41504819
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PURPOSE: This study investigated the anatomical and pathological mechanisms of immature squamous metaplastic epithelium in Weber's glandular ducts at the tongue base in human papillomavirus (HPV)-independent oropharyngea...PURPOSE: This study investigated the anatomical and pathological mechanisms of immature squamous metaplastic epithelium in Weber's glandular ducts at the tongue base in human papillomavirus (HPV)-independent oropharyngeal squamous cell carcinoma (OPSCC). METHODS: An analysis of 80 tongue base carcinoma cases clarified the anatomical connection to Weber's glands. Histological and immunohistochemical studies of these glandular ducts identified areas susceptible to cancer. A mouse model using 4-nitroquinoline-N-oxide was employed to simulate carcinogenic development. RESULTS: 42.5% of cases were linked to Weber's glands, with 20 directly connected to glandular ducts. Only one case was p16-positive, indicating that carcinogenesis in Weber's glandular ducts is largely non-HPV-mediated. The transformation zone with immature squamous metaplastic epithelium and CK17/p63+ reserve cells at Weber's glandular ducts were found, akin to cervical cancer susceptibility. CK17 studies indicated that the immature epithelium had "compromised barrier function" and "hyperproliferative activity", accelerating mutation and carcinogenesis. An atypical opening of the Weber's gland exposed the ductal epithelium to oncogenic factors, increasing carcinogenic risk. A mouse model confirmed the progression from metaplasia to carcinoma and the oncogenic potential of Weber's glandular ducts. CONCLUSIONS: Weber's glandular ducts are an important origin of HPV-independent OPSCC. The first animal model replicating this process offers an essential platform for studying HPV-independent OPSCC.
Steike DR, Pepper NB, Gravemeyer S
… +9 more, Bremer A, Glasbrenner B, Brüwer M, Pascher A, Domagk D, Biermann L, Lenz P, Eich HT, Reinartz G
J Cancer Res Clin Oncol
· 2026 Jan · PMID 41504807
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PURPOSE: Total neoadjuvant therapy (TNT) has demonstrated superior oncologic outcomes and improved organ preservation in randomized trials for locally advanced rectal cancer (LARC). This study aimed to assess the real-wo...PURPOSE: Total neoadjuvant therapy (TNT) has demonstrated superior oncologic outcomes and improved organ preservation in randomized trials for locally advanced rectal cancer (LARC). This study aimed to assess the real-world implementation of TNT in clinical routine and identify barriers to its application. METHODS: This retrospective, multicenter cohort study analyzed 111 patients with LARC treated between February 2021 and May 2024 across three certified colorectal cancer centers in Germany. Patients were stratified into TNT and non-TNT groups according to their neoadjuvant treatment modality. Primary endpoints included treatment adherence, disease-free survival (DFS), postoperative morbidity, and documented reasons for omitting TNT. Outcomes were compared with benchmark protocols from established TNT trials. RESULTS: Despite fulfilling guideline criteria, only 23 of 111 patients (20%) received TNT. Main barriers to TNT included advanced age, comorbidities, and patient refusal. The 1-year DFS rate was 96% in the TNT group and 94% in the non-TNT group. Severe low anterior resection syndrome (LARS) occurred in 9% of TNT patients compared to 22% in the non-TNT group. Postoperative complication rates were similar across both groups. While TNT was associated with favorable trends in disease control and functional outcomes, statistical significance was not reached. CONCLUSION: There is a notable discrepancy between clinical guideline recommendations and real-world TNT implementation in LARC. Addressing patient-specific barriers and adopting standardized, risk-adapted treatment decision frameworks may improve clinical integration of TNT, particularly in older and comorbid populations.
Hesse M, Iltzsche M, Nahhas D
… +3 more, Thomas C, Füssel S, Kind B
J Cancer Res Clin Oncol
· 2026 Jan · PMID 41504776
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PURPOSE: For non-muscle invasive bladder cancer (NMIBC), instillation with Bacillus Calmette-Guérin (BCG) is a standard therapy. With a still unclear mechanism, instillation activates the innate immune system, resulting...PURPOSE: For non-muscle invasive bladder cancer (NMIBC), instillation with Bacillus Calmette-Guérin (BCG) is a standard therapy. With a still unclear mechanism, instillation activates the innate immune system, resulting in an immunological effect on the tumour. The aim of this work was to investigate which bladder cancer (BLCA) cells can be activated by interferon (IFN) exposure. METHODS: The BLCA cell lines RT4 and SW780 were stimulated with IFN-α2, -β and -λ1 over 4-72 h. Quantitative PCR (qPCR) was used to determine the expression of IFN receptor subunits (RS) and selected interferon-stimulated genes (ISGs). Luciferase reporter assay was performed to detect the activation of the IFN responsive element (ISRE). Different signal transduction molecules of the JAK/STAT pathway were assessed by Western Blot to prove its activation in BLCA cells. The viability of the stimulated cells was measured by WST-1 assay and the apoptosis induction by caspase-3/7 assay. RESULTS: The JAK/STAT pathway was activated via the four RS. Upon long-term treatment, type I and type III IFNs significantly induced increased ISG expression and apoptosis induction of RT4 and SW780 cells, emphasising their antiproliferative and immunomodulatory activity. This activation was mediated by ISRE. IFN-β activated the JAK/STAT pathway with the greatest potency, highlighting its superior efficacy in modulating cellular responses in BLCA. CONCLUSION: Activation of the innate immune system has the ability to trigger further infiltration of the tumour microenvironment (TME) with immune cells, which positively influence the TME in its type, density and immunofunctional orientation against BLCA.
Oksuz S, Kinikoglu O, Ozkerim U
… +7 more, Isik D, Surmeli H, Ay S, Gundogdu UD, Basoglu T, Odabas H, Turan N
J Cancer Res Clin Oncol
· 2026 Jan · PMID 41504775
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BACKGROUND/OBJECTIVES: Malignant melanoma is an aggressive skin cancer with significant metastatic potential. Immune checkpoint inhibitors (ICIs), particularly those targeting the PD-1 pathway, have revolutionized treatm...BACKGROUND/OBJECTIVES: Malignant melanoma is an aggressive skin cancer with significant metastatic potential. Immune checkpoint inhibitors (ICIs), particularly those targeting the PD-1 pathway, have revolutionized treatment, improving survival rates. A PD-1 inhibitor, Nivolumab, has demonstrated durable responses in advanced melanoma patients. However, response variability necessitates predictive biomarkers for patient stratification. METHODS: The Gustave Roussy Immune Score (GRIm Score) is a prognostic tool integrating lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), and albumin levels to predict ICI efficacy. This retrospective study evaluated the association between the GRIm Score and response to nivolumab monotherapy in 40 patients with stage IV malignant melanoma treated between 2020 and 2024. Patients were classified into low-risk (score 0-1) and high-risk (score 2-3) groups. RESULTS: Results showed that patients with a low GRIm Score had significantly longer median progression-free survival (21.4 vs. 6.3 months, p = 0.003) and overall survival (26.5 vs. 7.2 months, p < 0.001). Multivariate analysis confirmed the GRIm Score as an independent prognostic factor (HR: 1.593, 95% CI: 1.156-2.197, p = 0.004), surpassing the predictive power of its components. CONCLUSIONS: This study is the first to validate the GRIm Score in malignant melanoma, suggesting it is a valuable biomarker for patient selection in immunotherapy trials. The findings highlight its potential in refining treatment decisions, though further validation in larger, multicenter cohorts is required.
Gong LP, Shao YT, Du Y
… +3 more, Sun LP, Tang LY, Chen JN
J Cancer Res Clin Oncol
· 2026 Jan · PMID 41504772
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BACKGROUND: Recent studies have found that Epstein-Barr virus (EBV) encodes circular RNAs (ebv-circRNAs) that are involved in tumorigenesis process in EBV-associated gastric carcinoma (EBVaGC). Since little is known whet...BACKGROUND: Recent studies have found that Epstein-Barr virus (EBV) encodes circular RNAs (ebv-circRNAs) that are involved in tumorigenesis process in EBV-associated gastric carcinoma (EBVaGC). Since little is known whether circRNAs can be enriched into exosomes and their functions in EBVaGC cancer stem cells (CSCs). METHODS: Exosomes from EBVaGC CSCs were isolated according to differential ultracentrifugation method. Expression patterns of ebv-circRNAs and human circRNAs in exosomes of EBVaGC CSCs were analyzed by RNA sequencing. CCK-8 assay, wound healing assay, transwell assay and apoptosis analysis were performed to explore the function of exosomes in EBVaGC CSCs. Data differences between two groups were evaluated using Student's t-test and survival analysis was performed by Kaplan–Meier methodology. RESULTS: Two circRNAs, ebv-circLMP2A and hsa-circRNF13 were enriched in EBVaGC CSCs derived exosomes, and positively associated with EBVaGC patients with metastasis. Bioinformatics analysis predicted that miR-5683 is the most likely potential target for both ebv-circLMP2A and hsa-circRNF13, and lower miR-5683 expression was positively correlated with microvessel density and Ki67 expression in clinical samples of EBVaGC. Cytology experiments preliminarily showed that EBVaGC CSCs derived exosomes significantly promoted the invasive growth of EBVaGC cells. CONCLUSIONS: Our findings suggest that exosomal circRNAs could be apromising diagnostic and therapeutic target for EBVaGC.
Li P, Li T, Huang M
… +10 more, Liu Y, Liu P, Wu Y, Li X, He R, Gan Y, Hong Y, Wang P, Lin J, Huang M
J Cancer Res Clin Oncol
· 2026 Jan · PMID 41501499
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BACKGROUND: Circulating tumor DNA (ctDNA) shows promise for predicting recurrence in colorectal cancer liver metastases (CRLM) patients. We investigated the prognostic value of perioperative ctDNA, particularly 2 week po...BACKGROUND: Circulating tumor DNA (ctDNA) shows promise for predicting recurrence in colorectal cancer liver metastases (CRLM) patients. We investigated the prognostic value of perioperative ctDNA, particularly 2 week postoperative minimal residual disease (MRD), in CRLM patients undergoing liver resection. METHODS: We prospectively collected blood samples from 94 CRLM patients before (after neoadjuvant therapy, if any) and 2 weeks after liver metastasectomy. 63 patients had both assessments. ctDNA status and variant allele fraction (VAF) were determined using targeted sequencing. Disease-free survival (DFS) was analyzed using Kaplan-Meier curves and Cox regression. Baseline characteristics were compared based on ctDNA status. RESULTS: Preoperative ctDNA status was not associated with DFS (p = 0.77). However, postoperative 2 week MRD status was a strong predictor; MRD-positive patients (N = 31) had significantly worse DFS than MRD-negative patients (N = 32) (p < 0.001). In multivariate analysis, postoperative MRD positivity (HR = 5.52, 95% CI: 2.46-12.39, p < 0.001) and multiple metastases (HR = 3.42, 95% CI: 1.42-8.25, p = 0.006) were independent predictors of DFS. Postoperative MRD positivity showed a trend towards association with higher primary tumor T stage (p = 0.095). Among MRD-negative patients, a higher maximum absolute VAF change (MaxΔVAF) suggested potentially worse DFS (p = 0.053), while it held no prognostic value in MRD-positive patients (p = 0.99). CONCLUSIONS: Postoperative 2 week ctDNA (MRD) status is a potent, independent predictor of DFS in resected CRLM patients and outperforms preoperative ctDNA. Early MRD assessment should be considered for risk stratification and may help guide adjuvant treatment decisions. VAF dynamics might further refine prognosis, especially in MRD-negative cases.
Zager JS, Orloff M, Ferrucci PF
… +18 more, Choi J, Eschelman DJ, Glazer ES, Ejaz A, Richtig E, Ochsenreither S, Reddy SA, Lowe MC, Beasley GM, Gesierich A, Gschnell M, Dummer R, Arance A, Fenwick SW, Sacco JJ, John J, Wheater M, Ottensmeier CH
J Cancer Res Clin Oncol
· 2025 Dec · PMID 41461960
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PURPOSE: To assess efficacy and safety in subgroups of patients treated with Melphalan/Hepatic Delivery System (melphalan/HDS), a drug/device combination for liver-directed treatment of metastatic UM (mUM) patients. Prev...PURPOSE: To assess efficacy and safety in subgroups of patients treated with Melphalan/Hepatic Delivery System (melphalan/HDS), a drug/device combination for liver-directed treatment of metastatic UM (mUM) patients. Previously reported FOCUS study results indicated melphalan/HDS treatment provides a clinically meaningful response rate and favorable benefit-risk ratio in patients with unresectable mUM. METHODS: Patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) every 6-8 weeks for up to 6 cycles. Post hoc analyses of efficacy and safety were conducted for patient subgroups based on demographic and baseline disease characteristics. RESULTS: 102 patients with mUM were enrolled; treatment was attempted in 95 patients; 91 patients received treatment. Subgroup analyses showed consistent tumor response regardless of age, sex, geographic region, presence/absence of extrahepatic lesions, and prior therapy. Patients with lower tumor burden had better objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) than those with higher tumor burden (ORR: 51.1 vs. 22.2%, p = 0.008; mPFS: 11.3 vs. 5.8 months, p = 0.007; mOS: 26.7 vs. 15.4 months, p = 0.008). Patients with 1-25% liver involvement had higher mOS than those with 26-50% liver involvement (22.4 vs. 16.9 months; p = 0.030); patients with low or normal lactate dehydrogenase (LDH) had higher mOS than those with elevated LDH (23.5 vs. 15.3 months; p = 0.019). The overall safety profile was similar across subgroups without evidence of cumulative toxicity with successive treatment cycles. CONCLUSION: Results demonstrate a favorable benefit-risk profile for melphalan/HDS across clinically relevant subgroups. However, early treatment in patients with low tumor burden may offer best results.
J Cancer Res Clin Oncol
· 2025 Dec · PMID 41452428
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PURPOSE: Postoperative gut dysbiosis and inflammation are common complications in ovarian cancer patients. This study aims to investigate the protective role of probiotic therapy on gut microbiota homeostasis and its pot...PURPOSE: Postoperative gut dysbiosis and inflammation are common complications in ovarian cancer patients. This study aims to investigate the protective role of probiotic therapy on gut microbiota homeostasis and its potential mechanism via activation of the ω-oxidation pathway. METHODS: We conducted a clinical analysis of ovarian cancer patients post-surgery who received probiotic therapy. Fecal samples were collected and analyzed using 16S rRNA sequencing to determine microbial diversity and composition. Metabolic pathway analysis was performed via MetaCyc. Additionally, an ovarian cancer mouse model was established to evaluate intestinal permeability, inflammatory cytokine levels, histopathological changes, and expression of ω-oxidation-related genes and proteins. The role of short-chain fatty acids (SCFAs) was also examined through combined administration with probiotics. RESULTS: Probiotic treatment significantly restored gut microbial diversity and reduced dysbiosis in post-surgical ovarian cancer patients. 16S rRNA sequencing revealed increased abundance of beneficial genera such as Alistipes, Roseburia, and Ruminococcus, while metabolic pathway analysis indicated significant activation of the ω-oxidation pathway. In mice, probiotic treatment reduced FD4 levels, restored intestinal barrier function, and modulated inflammatory cytokines by increasing IL-4 and IL-10 and decreasing IL-6 and TNF-α. Furthermore, probiotics upregulated expression of PPARα, CYP4F3, and CYP4A10 at both mRNA and protein levels, while reducing ROS and MDA levels, indicating alleviated oxidative stress. Combined treatment with SCFAs further enhanced these effects, suggesting a synergistic activation of ω-oxidation signaling and better restoration of gut homeostasis. CONCLUSION: Probiotic therapy effectively restores gut microbiota composition and intestinal integrity following ovarian cancer surgery, potentially through activation of the ω-oxidation pathway.