Search Results (849)

The concept of “platinum sensitivity” has long guided prognostic assessment and treatment selection in recurrent ovarian cancer. However, the emergence of targeted agents, such as bevacizumab and poly (ADP-ribose) polymerase inhibitors, has complicated its clinical utility. In contrast, emerging evidence suggests that platinum sensitivity may also be applicable to recurrent endometrial cancer. As in ovarian cancer, a prolonged platinum-free interval (PFI) in recurrent endometrial cancer is associated with an improved efficacy of subsequent platinum-based chemotherapy. The PFI is linearly correlated with the response rate to platinum re-administration, progression-free survival, and overall survival. Patients are typically classified as having platinum-resistant or platinum-sensitive disease based on a PFI cutoff of 6 or 12 months. However, unlike in ovarian cancer—where the duration of response to second-line platinum-based chemotherapy rarely exceeds the prior PFI (~3%)—approximately 30% of patients with recurrent endometrial cancer exhibit a sustained response to platinum rechallenge that extends beyond their preceding PFI. Despite the incorporation of immune checkpoint inhibitors into the treatment landscape of endometrial cancer, the role of platinum sensitivity in clinical decision-making—particularly regarding treatment sequencing and drug selection—remains a critical and unresolved issue. Further research is warranted to elucidate the mechanisms underlying platinum resistance and to guide optimal therapeutic strategies. 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

Mitomycin C (MMC) is a widely employed chemotherapeutic agent, particularly in non-muscle invasive bladder cancer (NMIBC), where it functions by inducing DNA cross-linking and promoting tumor cell apoptosis. However, the tumor microenvironment (TME) significantly influences the therapeutic efficacy of MMC. Among the key regulators within the TME, the complement system and the coagulation pathway play a crucial role in modulating immune responses to cancer therapies, including MMC. This article explores the interaction between platinum nanoparticles (PtNPs) with human serum (HS) of NMIBC patients (T1 and Ta subtypes) at three different points: before the chemotherapy instillation of MMC (t₀) and three (t₃) and six months (t₆) after the treatment with MMC. This novel nanoproteomic strategy allowed the identification of a TME proteomic signature associated with the response to MMC treatment. Importantly, two proteins involved in the immune response were found to be deregulated across all patients (T1 and Ta subtypes) during MMC treatment: prothrombin (F2) downregulated and complement component C7 (C7) upregulated. By understanding how these biomarker proteins interact with MMC treatment, novel therapeutic strategies can be developed to enhance treatment outcomes and overcome resistance in NMIBC. 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

Background/Objectives: Alterations in DNA damage repair mechanisms can impair the therapeutic effectiveness of cisplatin. MicroRNAs (miRNAs), key regulators of DNA damage repair processes, have been proposed as promising biomarkers for predicting the response to platinum-based chemotherapy (CT) in non-small cell lung cancer (NSCLC). In this study, by using a bioinformatics approach, we identified six miRNAs, which were differentially expressed (DE) between NSCLC patients characterized as responders and non-responders to platinum-based CT. We further validated the differential expression of the selected miRNAs on tumor and matched normal tissues from patients with resected NSCLC. Methods: Two miRNA microarray expression datasets were retrieved from the Gene Expression Omnibus (GEO) repository, comprising a total of 69 NSCLC patients (N = 69) treated with CT and annotated data from their response to treatment. Differential expression analysis was performed using the Linear Models for Microarray Analysis (Limma) package in R to identify DE miRNAs between responders (N = 33) and non-responders (N = 36). Quantitative real-time PCR (qRT-PCR) was used to assess miRNA expression levels in clinical tissue samples (N = 20). Results: Analysis with the Limma package revealed 112 DE miRNAs between responders and non-responders. A random-effects meta-analysis further identified 24 miRNAs that were consistently up- or downregulated in at least two studies. Survival analysis using the Kaplan–Meier plotter (KM plotter) indicated that 22 of these miRNAs showed significant associations with prognosis in NSCLC. Functional and pathway enrichment analysis revealed that several of the identified miRNAs were linked to key pathways implicated in DNA damage repair, including the p53, Hippo, PI3K and TGF-β signaling pathways. We finally distinguished a six-miRNA signature consisting of miR-26a, miR-29c, miR-34a, miR-30e-5p, miR-30e-3p and miR-497, which were downregulated in non-responders and are involved in at least three DNA damage repair pathways. Comparative expression analysis on tumor and matched normal tissues from surgically treated NSCLC patients confirmed their differential expression in clinical samples. Conclusions: In summary, we identified a signature of six miRNAs that are suppressed in NSCLC and may serve as a predictor of cisplatin response in NSCLC. Full article

Background/Objectives: Mutations in the BRCA1 and BRCA2 genes are well-known risk factors for ovarian cancer. They are also associated with response to platinum-based chemotherapy; however, their definitive impact on patient prognosis remains not fully understood. This study aimed to investigate the influence of BRCA mutation status on the age of ovarian cancer onset and on treatment outcomes in patients with high-grade serous ovarian cancer. Methods: This single-center retrospective analysis included newly diagnosed FIGO stage III and IV HGSOC patients treated between June 2018 and April 2023. Patients’ age, tumor histology, CA125 levels, BRCA mutation status, type of treatment (neoadjuvant or adjuvant chemotherapy), and surgical outcomes were collected and analyzed. Survival analyses were performed using the Kaplan–Meier method and log-rank test. Results: Pathogenic mutations were identified in 25 patients (15 in BRCA1, 10 in BRCA2). Patients with a BRCA mutation were diagnosed at a significantly younger age (median 58.78 years) compared to non-carriers (66.81 years; p < 0.001), with BRCA1 carriers being diagnosed the youngest (median 46.52 years). The study found no statistically significant difference in progression-free survival (PFS) between BRCA carriers and non-carriers. However, a significant improvement in overall survival (OS) was observed for patients with a BRCA1 mutation (p = 0.036). No significant OS difference was found for BRCA2 carriers. Conclusions: BRCA mutations, particularly in the BRCA1 gene, are associated with an earlier onset ovarian cancer. BRCA1 mutation appears to be a favorable prognostic factor for overall survival in patients with HGSOC. Our findings demonstrate the clinical implications of different BRCA mutations and support the need for further research in larger cohorts to confirm their influence on prognostic effects. Full article

Background/Objectives: Commonly characterized by limited metastatic sites, low tumor burden has been associated with favorable patient outcomes in various malignancies. However, its prognostic relevance in avelumab maintenance therapy for advanced urothelial carcinoma (UC) remains incompletely defined. Methods: We retrospectively analyzed 26 patients with advanced UC who received avelumab maintenance therapy following disease control with first-line platinum-based chemotherapy between March 2021 and May 2025. Patients were categorized by their metastatic pattern at a chemotherapy initiation: lymph node-only (as a surrogate for low tumor burden), non-visceral (excluding visceral organ involvement, but including bone), or visceral disease. Survival outcomes were assessed using the Kaplan–Meier method. Results: Among the cohort, 46.2% had lymph node-only metastasis and 57.7% had non-visceral disease. The median progression-free survival (PFS) and overall survival (OS) from the start of avelumab were 5.6 months and 21.7 months, respectively. OS from the initiation of platinum-based chemotherapy was 28.7 months. Patients with lymph node-only metastasis demonstrated significantly longer OS from chemotherapy initiation compared with those with other metastatic patterns (41.1 vs. 22.9 months, p = 0.044). However, the PFS and OS from avelumab initiation did not significantly differ. No survival benefit was observed for patients with non-visceral disease compared with those with visceral metastases. Conclusions: Lymph node-only metastasis, representing low tumor burden, was associated with significantly improved long-term survival in advanced UC patients undergoing avelumab maintenance following chemotherapy. These findings support the clinical utility of baseline tumor burden and metastatic pattern in risk stratification and shared decision-making for maintenance therapy in advanced UC. Full article

Cisplatin was the first metal-based anticancer drug introduced into clinical use. It is a “small” molecule, but it represented a very “big” discovery. Since it was introduced on the market, it has not been withdrawn, despite being not free of side effects, owing to its peculiarity of being highly effective in the treatment of cancer. Anticancer activity of the platinum-based complexes was discovered with this molecule; since then, several other platinum-based drugs have been developed and tested in preclinical studies against cancer cells; however, only a few of them reached clinical trials, and their side effects are not much less than cisplatin. Despite the constraints of drug resistance and side effects, chemotherapy remains a fundamental strategy in cancer treatment. Nowadays, cisplatin remains one of the most-used anticancer agents in treating lung, colon, ovary, testicles, bladder, cervix, and many more cancers, although cisplatin resistance represents a major hurdle in cancer treatment. Will there ever be another drug that can overcome the side effects of cisplatin but at the same time be able to block tumors as does cisplatin? Full article

The standard treatment for patients with locally advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiation. However, clinical responses are heterogeneous and generally not known until after the completion of therapy. Multiple studies have investigated imaging predictors (radiomics) for different cancer histologies, but little exists for NSCLC. The objective of this study was to develop a multivariate CT-based radiomics model to a priori predict responses to definitive chemoradiation in patients with lung adenocarcinoma. Methods: Patients diagnosed with locally advanced unresectable lung adenocarcinoma who had undergone chemoradiotherapy followed by at least one dose of maintenance durvalumab were included. The PyRadiomics Python library was used to determine statistical, morphological, and textural features from normalized patient pre-treatment CT images and their wavelet-filtered versions. A nested leave-one-out cross-validation was used for model building and evaluation. Results: Fifty-seven patients formed the study cohort. The clinical stage was IIIA-C in 98% of patients. All but one received 6000–6600 cGy of radiation in 30–33 fractions. All received concurrent platinum-based chemotherapy. Based on RECIST 1.1, 20 (35%) patients were classified as responders (R) to chemoradiation and 37 (65%) patients as non-responders (NR). A three-feature model based on a KNN k = 1 machine learning classifier was found to have the best performance, achieving a recall, specificity, accuracy, balanced accuracy, precision, negative predictive value, F1-score, and area under the curve of 84%, 70%, 80%, 77%, 84%, 70%, 84%, and 0.77, respectively. Conclusions: Our results suggest that a CT-based radiomics model may be able to predict chemoradiation response for lung adenocarcinoma patients with estimated accuracies of 77–84%. Full article

Background and Objectives: Epithelial ovarian cancer (EOC) remains the deadliest gynecologic malignancy, yet the psychosocial dynamics of early survivorship are inadequately described. We prospectively quantified six-month trajectories in the quality of life in a consecutive cohort of 88 women newly diagnosed with EOC and explored clinical moderators of change. Methods: Eighty-eight consecutive patients (mean age 59.1 ± 10.7 years) completed the SF-36, WHOQOL-BREF, EORTC QLQ-C30, and 10-item Perceived Stress Scale (PSS-10) at baseline (pre-therapy) and six months after cytoreductive surgery ± platinum-based chemotherapy. Stage (FIGO I–II vs. III–IV) and treatment pathway (primary debulking surgery, neoadjuvant chemotherapy plus interval debulking, chemotherapy only) data were recorded. Results: Global QoL improved significantly (EORTC Global Health +5.9 ± 7.7 points; p < 0.001) while perceived stress declined (ΔPSS −3.6 ± 5.1; p < 0.001). SF-36 Physical Functioning rose 4.7 ± 7.9 points (p < 0.001) and Mental Health 4.4 ± 7.9 points (p = 0.004). The WHOQOL Physical and Psychological domains gained 4.7 ± 7.1 and 4.3 ± 7.4 points, respectively (both p < 0.01). Advanced-stage patients experienced larger stress reductions than early-stage patients (−4.1 ± 2.7 vs. −2.9 ± 2.2; p = 0.028) but comparable QoL gains. Greater stress relief correlated with greater mental-health improvement (r = −0.51) and global-health gains (r = −0.45) (all p < 0.001). Treatment pathway did not significantly influence trajectories. Conclusions: Early survivorship after first-line ovarian-cancer therapy was characterized by the clinically meaningful recovery of physical and emotional functioning together with the moderate alleviation of perceived stress. Improvements were observed irrespective of stage and treatment strategy, suggesting that contemporary multimodal regimens do not inevitably compromise patient-reported outcomes. Our estimates provide preliminary effect sizes that should be validated in multi-center cohorts with longer follow-up. Full article

Background/Objectives: Germ cell tumors are the most common neoplasia in males < 50 y. In two case series, thromboembolic events (TEs) were reported in 8% and 13% of patients undergoing chemotherapy, whereas arterial thromboembolic events (ATEs) in other types of cancer treated with cisplatin had a frequency of 2% in a retrospective series and 0.67% in a meta-analysis. Recent data found a frequency of 2.4% for ATE in a large cohort of testicular cancer patients. Risk factors are not clearly identified, and given the severity of these events, further exploration is needed to determine appropriate preventive measures. Methods: We performed a retrospective cohort study of 171 patients undergoing chemotherapy for germ cell tumors in two centers in Switzerland and recorded the occurrence of ATE or venous thromboembolic events (VTEs) during chemotherapy or in the 3 months after its completion. Results: of 171 patients, 33.3% underwent adjuvant chemotherapy for stage I disease. Overall, 32 patients had a TE (18.7%, 95% CI 13.3–25.5%), 26 (15.2%, 95% CI 10.3–21.7%) had VTEs, and 11 (6.4%, 95% CI 3.4–11.5%) had ATEs. Five patients had both a VTE and ATE. VTEs were associated with disease stage (II, III, or relapse, with OR 15.6, p = 0.0002), retroperitoneal lymph nodes ≥ 3.5 cm (OR 3.2, p = 0.012), LDH > 500 UI/L (OR 5.3, p = 0.0025), and age > 35 y (OR 3.4, p = 0.005). The Khorana Score (KS) varied between 1 and 2 in 96% of the patients. ATEs were associated with active smoking (OR 6.5 p = 0.010), KS of ≥2 (OR 6.4 p = 0.004), and age > 35 y (OR 6.3, p = 0.01). Conclusions: Our findings show that ATEs are more frequent in our cohort than previous reports. We found a strong association between smoking and ATEs, which should be further assessed. Platinum-induced endothelial damage may be amplified by smoking in young patients in the absence of other risk factors and preventive medication. Full article

Background/Objectives: Response to immune checkpoint inhibitors (ICIs) is associated with several biological pathways, including tumor immunogenicity and antitumor immunity. Identifying host factors involved in these pathways may guide personalized ICI treatment. Methods: We describe the application of chromatin conformation assays to blood from patients with advanced urothelial carcinoma from the phase 3 JAVELIN Bladder 100 trial (NCT02603432). This trial demonstrated a significant survival benefit with avelumab maintenance plus best supportive care (BSC) vs. BSC alone following non-progression with platinum-based chemotherapy as first-line therapy. Blood-based chromatin conformation markers (CCMs) were screened for associations with high/low immune effector gene expression in tumors and for interactions with outcomes and tumor mutation burden. Results: Candidate CCMs included genes involved in several immune response pathways, such as POU2F2, which encodes a transcription factor that regulates B-cell maturation. Conclusions: Our findings suggest that polygenic host factors may affect response to ICIs and support further investigation of chromatin conformation assays. Full article

Resectable non-small cell lung cancer (NSCLC) continues to pose significant challenges with high recurrence and mortality rates, despite traditional platinum-based chemotherapy yielding only an approximate 5% improvement in 5-year overall survival when administered preoperatively or postoperatively. In recent years, the integration of immune checkpoint inhibitors (ICIs), such as nivolumab, durvalumab and pembrolizumab, with platinum-based regimens in the perioperative setting has emerged as a transformative strategy. Our comprehensive review, based on a systematic bibliographic search of PubMed, Google Scholar, EMBASE, Cochrane Library, and clinicaltrials.gov, targeting pivotal clinical trials from the past two decades, examines the impact of these neoadjuvant and adjuvant chemoimmunotherapy approaches on major pathological response rates and overall survival in early-stage NSCLC. Although these perioperative strategies represent a paradigm shift in treatment, promising durable responses are offset by persistent recurrence, emphasizing the necessity for optimized treatment sequencing, duration, and the identification of predictive biomarkers. Collectively, our findings underscore the critical role of the perioperative schema, particularly the neoadjuvant component, which enables the evaluation of novel biomarkers as surrogates for overall survival, in improving patient outcomes and delineating future research directions aimed at reducing mortality and enhancing the quality of life for patients with resectable NSCLC. Full article

Platinum-induced ototoxicity constitutes a significant adverse effect in pediatric oncology, frequently resulting in permanent hearing impairment with profound implications for quality of life, language acquisition, and scholastic performance. This comprehensive review critically evaluates contemporary ototoxicity monitoring practices across various pediatric oncology settings, analyzes current guideline recommendations, and formulates strategies for implementing standardized surveillance protocols. Through examination of recent literature—encompassing retrospective cohort investigations, international consensus recommendations, and functional outcome assessments—we present an integrated analysis of challenges and opportunities in managing chemotherapy-associated hearing loss among childhood cancer survivors. Our findings demonstrate marked heterogeneity in monitoring methodologies, substantial implementation obstacles, and considerable impact on survivors’ functional status across multiple domains. Particularly concerning is the persistent absence of an evidence-based consensus regarding the appropriate duration of audiological surveillance for this vulnerable population. We propose a structured framework for comprehensive ototoxicity management emphasizing prompt detection, standardized assessment techniques, and integrated long-term follow-up care to minimize the developmental consequences of platinum-induced hearing impairment. This approach addresses critical gaps in current practice while acknowledging resource limitations across diverse healthcare environments. Full article

Background/objectives: Despite advancements in early diagnosis and clinical practices guided by standardized care protocols, Merkel cell carcinoma (MCC) is marked by an unfavorable prognosis with a 5-year relative survival rate of 65%, based primarily on data collected prior to the introduction of immunotherapy. Regional nodal metastases affect 40–50% of MCC patients, while approximately 33% experience distant dissemination. Among these, bone and bone marrow metastases are particularly notable, although the characteristics and clinical implications of this metastatic disease in MCC remain poorly understood. Methods: A comprehensive review was conducted using the Medline database (via PubMed) up to January 2025. The search strategy included the string “(Merkel cell carcinoma AND (bone OR marrow))”. Results: A total of 1133 (69.3% male and 30.7% female) patients diagnosed with advanced MCC were collected. The median (IQR) age at diagnosis was 67.5 (12.65) years old. Overall, 201 (20.8%) cases of bone and/or bone marrow metastases were identified and linked to a primary known MCC in 75.7% of cases. Bone metastases (BMs) appear as the third most common metastatic site, following the liver (second) and lymph nodes (first). They show mixed biological and radiological behavior, with a marked preference for the axial skeleton over the appendicular one. Addressing the characteristics of metastatic bone disease, neurological symptoms were the most documented, whereas bone marrow involvement and leukemic spread seemed to be primarily related to immunosuppression. Multimodal treatment strategies, including platinum-based chemotherapy and radiotherapy, were the primary approaches adopted, reflecting therapeutic practices from the pre-immunotherapy era. Conclusions: The pattern of metastatic spread in MCC differs among studies, with the bones resulting as the third most common site of distant spread. Excluding head and neck MCC, which seems to be more regularly associated with liver metastases, the relationship between the primary tumor site and the development of bone or bone marrow metastases appears inconsistent. Overall, BMs mostly correlated with advanced MCC stages and poorer survival outcomes, with a median overall survival (OS) of 8 months (range 12.75–4). The integration of international guidelines, evolving evidence from clinical trials, and the expanding role of immune checkpoint inhibitors (ICIs) will contribute to improving systemic disease control and enhance patient care. Full article