Platinum Research Articles (Page 1)

Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) is widely used for biomolecular mapping but has not been extensively applied for direct element imaging. Established techniques such as LA-ICP-MS and SIMS provide high sensitivity for elemental analysis but lack the ability to simultaneously map elements and biomolecules. Here, we demonstrate the feasibility of MALDI MSI for direct spatial element profiling across multiple biological contexts. We optimized MALDI MSI parameters─including laser power, ionization conditions, and mass resolving power─to enable the detection of endogenous and exogenous elements such as Fe, Ca, Gd, Pt, and Cl. Using a combination of high-resolution FTICR-MS and timsTOF MSI, we assessed ionization efficiency, spectral fidelity, and isotopic accuracy. The method was applied to murine developmental models, genetic metal accumulation disorders, and platinum-based chemotherapy distributions in tumors. Our results demonstrate that MALDI MSI enables element detection while preserving spatial integrity. Computational modeling and spectral similarity analysis confirmed the reliability of isotopologue distributions. These findings establish MALDI MSI as a viable alternative for high-resolution element imaging, offering a complementary approach to LA-ICP-MS and SIMS by integrating atomic and biomolecular spatial distributions. This method expands the analytical capabilities of MALDI MSI and opens new avenues for metallomics, pharmacokinetics, and disease biomarker research.

First-line chemo-immunotherapy has significantly improved survival in extensive-stage small-cell lung cancer (ES-SCLC). However, rapid disease progression still occurs, with a median progression-free survival (PFS) of only 4.5-5.8 months from induction therapy. We initiated two single-arm, phase II studies to assess the first-line maintenance therapy with tislelizumab plus anti-angiogenic drugs following induction therapy in ES-SCLC patients. Previously untreated ES-SCLC patients were enrolled to receive tislelizumab plus platinum-based chemotherapy as induction therapy for 4 cycles, followed by tislelizumab plus sitravatinib (Trial 1) or anlotinib (Trial 2) as maintenance therapy in a 21-day cycle. The primary endpoint was the 1-year PFS rate in the maintenance analysis set (MAS, including patients receiving ≥1 dose of maintenance therapy). Outcomes in MAS were calculated from the start of maintenance therapy. Twenty-one patients were enrolled, and 18 patients entered the maintenance phase in each trial. From the start of the maintenance therapy, the median PFS was 6.4 and 7.8 months (1-year PFS rates of 22.2% and not reached), respectively; the median overall survival (OS) was 18.3 months and not reached. From induction therapy, the corresponding median PFS was 9.1 and 10.8 months, with a median OS of 17.6 months and not reached. In MAS, the most common grade ≥3 treatment-related adverse events (TRAEs) included hypertension (22.2%) in Trial 1 and fatigue (5.6%) in Trial 2. No patients died from TRAEs in either trial. Maintenance therapy with tislelizumab plus sitravatinib or anlotinib yielded clinically meaningful survival results and was generally well tolerated in ES-SCLC, warranting further exploration in larger-scale trials.

Pemetrexed demonstrates significant efficacy and safety in second-line and single-agent maintenance therapies, and in combination with platinum-based chemotherapy, it serves as the standard first-line treatment for driver-negative advanced non-small cell lung cancer (NSCLC). Although several studies have reported its widespread use and associated adverse effects, reports of pemetrexed-related pigmentation are rare. At present, the mechanism underlying pemetrexed-induced pigmentation remains unknown, and the timing of onset and risk factors are unclear. Here, we report a case of left lung adenocarcinoma (cT2bN2M1 IVB) with bone metastasis. After the third cycle of pemetrexed, pigmentation, numbness, pain, and walking difficulty developed on both feet and the dorsum of the ankles. These symptoms gradually worsened with subsequent chemotherapy cycles. Following neurotrophic treatment with diclofenac sodium gel and mecobalamin, numbness and pain improved, while pigmentation subsided gradually after discontinuation of pemetrexed. In addition, this study retrospectively analyzed nine patients with pemetrexed-induced skin pigmentation and found that the median onset was during the second cycle (range: 1–17 cycles). Pigmentation could be widely distributed on the body surface and aggravated with continued pemetrexed therapy. However, pigmentation resolved spontaneously after discontinuation, with individual differences.

Immune checkpoint inhibitors (ICIs) are a standard treatment for advanced non-small-cell lung cancer (NSCLC), but limited data exist regarding their use in patients with HIV-positive. This study evaluated the efficacy and safety of ICI-based therapy in this population. In this single-center, comparative study, 18 patients with treatment-naive advanced NSCLC with HIV (experimental group) and 40 HIV-negative controls (control group) received 4-6 cycles of tislelizumab plus platinum-based chemotherapy, followed by tislelizumab maintenance until disease progression or unacceptable toxicity. A higher incidence of tuberculosis was observed in the experimental group compared with the control group (33.3 vs. 20.0%). The objective response rate was 77.8% [95% confidence interval (CI): 56.5-99.1] in the experimental group and 77.5% (95% CI: 64-91) in the control group ( P = 0.981). The 6-month progression-free survival rate was 83.3% (95% CI: 64.3-99.9) for the experimental group and 82.5% (95% CI: 70.2-94.8) for the control group ( P = 0.227). The 6-month overall survival rate was 88.9% (95% CI: 72.8-99.9) in the experimental group and 97.5% (95% CI: 92.4-99.9) in the control group ( P = 0.192). The incidences of grade 3 or higher adverse events were 38.9 and 32.5% in the experimental and control groups, respectively. One patient in the experimental group died due to a serious opportunistic infection. Immunotherapy combined with chemotherapy showed comparable efficacy and safety in patients with advanced NSCLC irrespective of HIV status. Patients with HIV-positive had a higher tendency for opportunistic infections, including tuberculosis.

First-line maintenance therapy with poly(adenosine diphosphate-ribose) polymerase inhibitors (PARP inhibitors) after platinum-based chemotherapy improves progression-free survival (PFS) in advanced epithelial ovarian cancer (EOC), particularly in patients with BRCA-variant or homologous recombination-deficient tumors. However, overall survival (OS) benefits remain uncertain, and toxic effect profiles emphasize the need for optimized patient and agent selection. To evaluate the efficacy and safety of first-line PARP inhibitor maintenance therapy compared with chemotherapy alone in advanced-stage EOC, with subgroup analyses by BRCA and HRD status, up-front or interval surgery, chemotherapy response, and residual disease. Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from database inception to August 19, 2024. Randomized clinical trials and prospective 2-arm studies evaluating PARP inhibitor maintenance therapy in patients with advanced-stage EOC responding to first-line platinum-based chemotherapy were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed in reporting this study. Data were independently extracted by 2 reviewers. Random-effects models were used for meta-analysis. Risk of bias was assessed with Cochrane risk of bias and certainty of evidence with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Primary outcomes were PFS and OS; secondary outcomes included high-grade adverse events. A total of 7 randomized clinical trials with 4013 patients with advanced-stage epithelial ovarian cancer responding to first-line platinum-based chemotherapy were included. PARP inhibitor maintenance was associated with improved PFS in the overall population (hazard ratio [HR], 0.57; 95% CI, 0.46-0.70; high certainty) and in all molecular subgroups except the homologous recombination proficient group (BRCA variant: HR, 0.40; 95% CI, 0.35-0.45; BRCA wild type: HR, 0.62; 95% CI, 0.44-0.86; homologous recombination deficient: HR, 0.44; 95% CI, 0.39-0.50; all high certainty). PFS benefits were consistent across surgical timing, chemotherapy responses, and residual disease; for example, surgical timing had HRs of 0.51 (95% CI, 0.31-0.84) for neoadjuvant chemotherapy and 0.54 (95% CI, 0.36-0.81) for primary cytoreductive surgery (all high certainty). No molecular subgroup showed a statistically significant OS improvement (high to low certainty). High-grade adverse events were more common in the PARP inhibitor group (HR, 2.40; 95% CI, 1.16-4.93; high certainty). Observed treatment efficacy and toxic effects varied across PARP inhibitor regimens; for example, the risk ratio for any recurrence or death in the overall study group ranged from 0.53 (95% CI, 0.40-0.70) for senaparib to 0.83 (95% CI, 0.68-1.00) for olaparib, while the risk ratio for high-grade adverse events ranged from 1.15 (95% CI, 0.64-2.06) for veliparib to 4.73 (95% CI, 2.77-8.07) for niraparib. In this study, no subgroup showed an association between first-line PARP inhibitor maintenance therapy in advanced-stage EOC and improved OS, and findings suggest that the consistency of associated PFS benefits may vary, particularly in homologous recombination proficient and BRCA wild type tumors. Variability in efficacy and toxic effects across subgroups and PARP inhibitor regimens underscores the importance of individualized treatment decisions.

Low-grade serous ovarian carcinoma (LGSOC) is a rare and clinically distinct subtype of ovarian cancer, which presents unique challenges in diagnosis and treatment. LGSOC is characterized by low proliferation rates, high expression of hormone receptors, and frequent alterations in the mitogen-activated protein kinase (MAPK) pathway. Initial standard treatment includes cytoreductive surgery followed by platinum-based chemotherapy and endocrine therapy. However, high recurrence rates (~80%) and poor responses to chemotherapy underscore the urgent need for new treatment strategies. Endocrine therapy is being investigated in the upfront setting, and recent advances in targeted therapies, including MAPK pathway inhibitors and investigational agents such as cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, are shaping the evolving LGSOC treatment landscape. Notably, the recent US Food and Drug Administration approval of the avutometinib/defactinib combination for KRAS-mutated recurrent LGSOC marks a significant milestone in targeted therapy for this disease. Despite these advances, challenges remain in optimizing sequencing strategies and overcoming acquired resistance. This review addresses the importance of understanding the distinct pathophysiology of LGSOC, diagnostic challenges, limitations of conventional treatments, and evolving therapeutic approaches in LGSOC.

Bladder cancer is a prevalent and costly malignancy characterized by significant heterogeneity in presentation and clinical outcomes. This study aimed to classify the molecular subtypes of bladder cancer using immunohistochemistry (IHC) and to evaluate the prognosis, treatment responsiveness, and clinical utility of IHC-based subtype classification. We retrospectively reviewed the data of 84 patients with bladder cancer who underwent radical cystectomy. Immunohistochemistry was performed using the markers CK5/6, CK14, CK20, GATA3, and UPK2. Molecular subtypes were identified through hierarchical clustering, and statistical analyses were conducted to evaluate cancer-specific survival (CSS) and recurrence-free survival (RFS). Among the 68 patients included in the final analysis, 52 were classified as luminal type and 16 as basal type. The 5-year CSS and RFS were 76.2% and 64.2%, respectively. Among patients who received platinum-based neoadjuvant chemotherapy, those with the luminal subtype showed significantly better RFS than those with the basal subtype (P=0.016, HR 5.27, 95%CI 1.15-24.1). However, no significant difference in CSS was observed between the luminal and basal subtypes. Molecular subtypes can be inferred using common immunohistochemical markers, providing a practical approach for personalized treatment strategies. Further prospective studies are needed to validate these findings.

BackgroundThe evolution of neoadjuvant therapies for resectable head and neck squamous cell carcinoma (HNSCC) has accelerated with the advent of immune checkpoint inhibitors. While platinum-based induction chemotherapy (ICT) shows modest benefits, emerging neoadjuvant immunotherapy has demonstrated unprecedented pathological response rates (PRR) in early-phase trials. However, significant controversy persists regarding the survival benefits and optimal integration of these strategies into multimodality paradigms. This umbrella review synthesizes meta-analytical evidence to evaluate whether neoadjuvant immunotherapy or chemotherapy confers clinically meaningful advantages in surgical outcomes and long-term survival for resectable HNSCC.MethodsWe conducted an umbrella review of systematic reviews and meta-analyses (SRMAs) evaluating neoadjuvant immunotherapy or chemotherapy in resectable HNSCC (PubMed, Embase, Cochrane Library; January 2016–March 2025, no language restriction). Critical endpoints included pathological complete response (PCR), major pathological response (MPR), disease control rate (DCR), objective response rate (ORR), treatment-related adverse events (TRAEs), progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS). Methodological rigor was assessed using AMSTAR-2 (A Measurement Tool to Assess systematic Reviews 2), and GRADE (Grading of Recommendations Assessment, Development and Evaluation) with sensitivity analyses performed for corrected covered area (CCA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 for s (PRISMA 2020 for s) checklist was followed.ResultsA total of 10 systematic reviews with meta-analyses were included, with a cumulative patient population of 15,871. Neoadjuvant anti-PD-(L)1 + chemotherapy achieved PCR rates of 26.7–30.1%. Neoadjuvant anti-PD-(L)1 + radiotherapy yielded the highest downstaging rate of 93.3% (95% confidence interval [CI], 68.1–99.8%) and ORR of 57.0% (95%CI, 44.0–72.0%). Neoadjuvant immunotherapy showed 1-year OS of 84.0–89.7%, though 3-year OS converged to 78.9% (95%CI, 63.2–89.1%). ICT showed marginal benefits in locoregional control (hazard ratio [HR], 0.59; 95%CI, 0.42–0.85) but had limited impact on overall survival (HR, 1.16; 95%CI, 1.07–1.26). However, these efficacy benefits must be balanced against a significant risk of Grade 3–4 TRAEs of 9.7–35.0%.ConclusionsNeoadjuvant anti-PD-(L)1 + radiotherapy offers superior pathological and early survival outcomes in resectable HNSCC, supporting its integration into treatment algorithms. However, the lack of high-quality evidence regarding this treatment limits definitive conclusions. Further trials are needed to validate long-term benefits and guide biomarker-driven patient selection.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-025-04441-z.

Objectives: Lung cancer is most commonly caused by smoking, and unfortunately, a significant portion of patients continue to smoke even during their treatment. Our study aimed to investigate the impact of current smoking on the treatment response in patients receiving nivolumab. Methods: This was a retrospective cohort study that compared the treatment responses of patients who continued to smoke during nivolumab therapy and those who had a history of smoking but had quit prior to nivolumab initiation. The study included 55 patients with advanced non-small cell lung cancer who received treatment between 2019 and 2025. All participants had stage 4 disease and had progressed after initial platinum-based combination chemotherapy. The treatment responses were categorized as progressive disease, stable disease, partial response, and complete response, and the differences between current smokers and ex-smokers were analyzed, with the response evaluation conducted according to the PET Response Criteria in Solid Tumors 1.0 guidelines. Results: The analysis revealed a statistically significant difference in treatment response between ex-smokers and current smokers (P=0.039). Ex-smokers demonstrated superior Objective Response Rates (56.0% vs. 25.0%) and Disease Control Rates (76.0% vs. 33.3%) compared to current smokers, with the difference in Disease Control Rate reaching statistical significance (P=0.042). Furthermore, multivariate logistic regression indicated that current smokers were 3.64 times less likely to achieve an objective response to nivolumab than ex-smokers, a finding that, while borderline significant, suggests a clinically meaningful trend (P=0.084). Conclusions: Our study demonstrated that continued smoking during nivolumab therapy may negatively impact the treatment response. While more prospective data is needed, the current results and existing literature suggest that smoking cessation is crucial for patients receiving nivolumab, and clinicians should be more vigilant in addressing this issue.

Background Reliable biomarkers are urgently needed to predict response to immune checkpoint inhibitors in metastatic esophageal adenocarcinoma (mEAC). This study evaluated early circulating free DNA (cfDNA) dynamics as a predictor of treatment response and survival in patients receiving platinum-based chemotherapy plus Nivolumab. Methods In this prospective pilot study, 95 patients with mEAC were treated with Nivolumab and platinum-based chemotherapy. Plasma cfDNA levels were measured at baseline, Day 15, and Day 30 using digital droplet PCR. The primary outcome was objective treatment response; secondary outcomes included progression-free survival (PFS) and overall survival (OS). Tumor mutational burden (TMB), PD-L1 expression, liver metastasis, and ECOG status were also assessed. Results Patients with a cfDNA Day 30/Baseline ratio <0.4 had significantly improved median PFS (11 vs. 4 months) and OS (14 vs. 7 months) compared to those with ratios >0.8 (p for trend <0.001). Early decline in cfDNA correlated with treatment response. High TMB (≥10 mut/Mb) was independently associated with increased response (adjusted OR: 2.5, 95% CI: 1.2–5.2, p=0.015). ECOG >1 was inversely associated with response (adjusted OR: 0.35, p=0.01). PD-L1 expression and liver metastasis were not significantly predictive. Conclusion Early cfDNA kinetics—particularly a Day 30/Baseline ratio <0.4—strongly predicted response and survival in mEAC patients receiving chemoimmunotherapy. cfDNA monitoring offers a promising non-invasive tool for early treatment stratification and response assessment in this population.

Abstract Extragonadal germ cell tumors (EGGCTs) are rare malignancies that arise outside the gonads and occur infrequently in the gastrointestinal tract. Their presentation often mimics that of other abdominal neoplasms, posing diagnostic challenges. Histopathological and immunohistochemical confirmation, along with tumor marker evaluation, is essential for diagnosis. Early diagnosis and platinum-based chemotherapy can significantly improve patient outcomes. A 25-year-old male presented with abdominal pain, a palpable mass in the umbilical region, and subacute intestinal obstruction. Imaging revealed a heterogeneously enhancing lesion in the mesentery and a subcapsular lesion in the left kidney. Emergency debulking surgery was then performed. Histopathology and immunohistochemistry confirmed an EGGCT favoring a yolk sac tumor. Serum marker levels were elevated with AFP (alpha-fetoprotein) of 854 IU/mL, 23 mIU/mL of β-human chorionic gonadotrophin (β-hCG); 277 U/L of LDH. Ultrasonography of the testes revealed microcalcifications in the left testis, without overt malignancy. The patient was diagnosed with a Stage IIIC extragonadal non-seminomatous germ cell tumor. He was started on an EP regimen owing to poor pulmonary function, followed by BEP, and was scheduled for a high inguinal orchidectomy. This case highlights the importance of including EGGCTs in the differential diagnosis of abdominal masses in young males. A multidisciplinary approach with timely histological and oncological assessments is vital. Early intervention with platinum-based chemotherapy offers a favorable prognosis, even in advanced stages. Given the rarity of this presentation, further studies are needed to refine diagnostic and therapeutic strategies.

Objective: Non-small cell lung cancer (NSCLC) is a common and deadly cancer, and predicting survival can be useful for guiding treatment. This study aimed to investigate the impact of metabolic status-specifically resting energy expenditure (REE)-and clinicopathological characteristics on survival outcomes in patients with metastatic NSCLC receiving nivolumab as second-line therapy following platinum-based chemotherapy. Methods: This prospective, non-interventional, observational, single-center study included 148 adult patients with metastatic NSCLC receiving nivolumab as second-line treatment. Demographic data, cancer diagnosis-related characteristics, laboratory parameters, measured REE (mREE), and predicted REE (pREE) were recorded just before nivolumab treatment was initiated. Results: The mean ages of non-hypermetabolic and hypermetabolic patients were 63 ± 8 and 64 ± 9, respectively. Weight, height, BMI, and pREE were significantly higher in the non-hypermetabolic group. In the hypermetabolic group, the incidence of brain metastasis and the mREE were significantly higher. The median progression-free survival (PFS) and overall survival (OS) were 5.3 and 15.8 months, respectively. Multivariate analysis identified several predictors of survival. Poor ECOG performance status (PS) (p < 0.001), liver metastases (p = 0.018), and mREE/pREE ratio > 120% (p = 0.005) were significantly associated with shorter PFS. Similarly, poor ECOG PS (p = 0.037), liver metastases (p = 0.041), and mREE/pREE ratio > 120% (p = 0.009) were also linked to reduced OS. Conclusions: In patients with NSCLC treated with nivolumab, poor ECOG PS, the presence of liver metastases, and an mREE/pREE ratio > 120% were associated with poorer survival outcomes. Further prospective multicenter studies are required to validate these findings.

Treatment options for patients with advanced non-small cell lung cancer (NSCLC) with disease progression following immune checkpoint inhibitor (ICI) and platinum-based chemotherapy are limited. GT103 is a fully human immunoglobulin G3 monoclonal antibody targeting complement factor H, which promotes antitumor immunity. In a Phase I study, GT103 was well tolerated and maximum tolerated dose was not reached. A single arm, Simon two-stage, Phase II study was conducted that evaluated efficacy and safety of GT103 plus pembrolizumab in patients with advanced NSCLC who have had progression on up to two lines of therapy, including an ICI. Patients with actionable genomic drivers were eligible if they had received at least one targeted therapy. Patients received GT103 10 mg/kg and pembrolizumab 200 mg intravenously every 3 weeks until disease progression or unacceptable toxicity. Primary objectives were safety and objective response rate. Secondary objectives were overall survival and progression-free survival. Twenty-one patients were enrolled. Most common treatment-related adverse events occurring in ≥10% of patients were fatigue (24%, n=5) and decreased lymphocyte count (24%, n=5). One patient experienced grade 3 treatment-related adverse events, including pneumonitis and decreased lymphocyte count. Objective response rate was 10% (95% CI, 1-30) with two objective responses (1 complete response (CR), 1 partial response (PR)). Disease control rate (=CR+PR+stable disease (SD)) was 67% (n=14). Four patients (19%) experienced disease control for over 9 months. Median progression-free survival was 2.6 months (95% CI, 1.4-4.0) and median overall survival was 10.3 months (95% CI, 6.6-NE). Combination of GT103 with pembrolizumab was well tolerated with no new safety signals. A subset of patients experienced durable responses and disease control despite prior exposure to ICI.

Radiotherapy-free pembrolizumab combined with chemotherapy for locally advanced non-small-cell lung cancer with PD-L1 tumour proportion score of 50% or higher (Evolution trial): a multicentre, single-arm, phase 2 study.

Towards a new approach in pleural mesothelioma: Perioperative immunotherapy and its implications.

Immune checkpoint inhibitor-induced interstitial lung disease with and without CTLA-4 regimen in non-small cell lung cancer patients and PD-L1<1%: A multicenter, retrospective study.

Pancreatic panniculitis associated with presumed advanced pancreatic tumor: A case report and literature review.

Real-world treatment patterns, healthcare resource utilization, and healthcare costs in patients in the United States with metastatic non-small cell cancer receiving second or subsequent line systemic anticancer therapy.

Outcomes with neoadjuvant osimertinib and/or chemotherapy in patients with EGFR-mutant resectable non-small cell lung cancers.

Exploring Biginelli hybrids in the AI-driven development of ruthenium complexes: Anticancer activity, DNA/HSA binding study, impacts on apoptosis and BCL-2/BCL-XL suppression.