Search Results (469)

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

Chemotherapeutic agents and radiotherapy are highly effective in treating malignancies. However, they carry a significant risk of harming the gonads and may lead to endocrine dysfunction and reproductive issues. This review outlines the molecular mechanisms of gonadotoxic therapies, focusing on radiation, alkylating agents, and platinum compounds. It discusses the loss of PMFs due to gonadotoxic exposure, including DNA double-strand breaks, oxidative stress, and dysregulated signaling pathways like PI3K/PTEN/Akt/mTOR and TAp63-mediated apoptosis. Furthermore, it explores strategies to mitigate gonadal damage, including GnRH agonists, AMH, imatinib, melatonin, sphingolipid metabolites, G-CSF, mTOR inhibitors, AS101, and LH. These therapies, paired with existing fertility preservation methods, could safeguard reproductive and hormonal functions and improve the quality of life for young cancer patients. Despite the progress made in recent years in understanding gonadotoxic mechanisms, gaps remain due to questionable reliance on mouse models and the lack of models replicating human ovarian dynamics. Long-term studies are vital for wider analyses and exploration of protective strategies based on various animal models and clinical trials. It is essential to verify that these substances do not hinder the anti-cancer effectiveness of treatments or cause lasting DNA changes in granulosa cells, raising the risk of miscarriages and infertility. 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

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: In September 2021, pemigatinib received Health Canada approval for previously treated locally advanced/metastatic cholangiocarcinoma (CCA) with FGFR2 rearrangements/fusions. This retrospective study aimed to characterize the real-world management and outcomes of patients with CCA receiving pemigatinib through a Canadian patient support program (PSP). Methods: We evaluated a multi-centre case series of Canadian patients who were prescribed pemigatinib between September 2021 and January 2023 for eligible CCA diagnoses and enrolled in the PSP. The retrospective study data included demographic and disease-, treatment-, and outcome-related information, and these were collected using a survey of prescribing physicians. Results: Of the 26 patients who initiated pemigatinib in the PSP, we received survey responses for 18 (69%). Their median age was 57 years, 67% were female, 61% had stage IV disease, and 83% had intrahepatic CCA. Prior to pemigatinib, a partial hepatectomy was performed in 44% of the patients, and 66% of the patients received 2–4 prior lines of systemic therapy. All patients were treated with platinum-based regimens as the first-line treatment for unresectable/metastatic disease. The median follow-up time on pemigatinib was 12.6 (range: 2.3–28.4) months, and their median real-world progression-free survival (rwPFS) was 12.1 months (95% CI 7.2-NR). The physician-assessed objective response and disease control rates were 56% and 89%, respectively. For the nine patients who discontinued pemigatinib, the median treatment duration was 10.6 months (range: 0.8–21.7). Disease progression was the most common reason for discontinuation (89%). None discontinued due to adverse events. Conclusions: Objective response rates, disease control rates, and a PFS comparable to that in the phase 2 FIGHT-202 trial was reported with pemigatinib use in this Canadian PSP cohort. 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

Small-cell lung cancer (SCLC) is an aggressive malignancy with poor prognosis despite initial responsiveness to chemotherapy. Platinum-based chemotherapy with etoposide has long been the standard first-line treatment, but recent advances in immunotherapy have improved outcomes. Phase III trials, including IMpower133 and CASPIAN, demonstrated that adding immune checkpoint inhibitors, such as atezolizumab and durvalumab, to chemotherapy significantly enhances overall survival (OS) and progression-free survival (PFS). This case report describes a 76-year-old former smoker diagnosed with extensive-stage SCLC (ES-SCLC) following the detection of a left lower lung mass. The patient underwent combination therapy with carboplatin, etoposide, and atezolizumab, followed by maintenance atezolizumab. The patient demonstrated a sustained response to treatment, with significant tumor regression and no evidence of disease progression. Despite advanced age and comorbidities, treatment was well-tolerated, with no severe adverse events. Serial imaging over 24 months confirmed sustained disease stability, with regression of mediastinal lymphadenopathy and no new lesions. This case highlights the potential for prolonged disease control in select SCLC patients treated with chemo-immunotherapy. The absence of significant toxicities underscores the feasibility of immunotherapy even in elderly patients with comorbidities. These findings support the role of atezolizumab as a key component of ES-SCLC treatment and suggest the need for further research on predictors of durable response. Full article

Developments of nanostructured materials have a significant impact in various areas, such as energy technology and biomedical use. Examples include solar cells, energy management, environmental control, bioprobes, tissue engineering, biological marking, cancer diagnosis, therapy, and drug delivery. Currently, researchers are designing multifunctional nanodrugs that combine in vivo imaging (using fluorescent nanomaterials) with targeted drug delivery, aiming to maximize therapeutic efficacy while minimizing toxicity. These fascinating nanoscale “magic bullets” should be available in the near future. Inorganic nanovehicles are flexible carriers to deliver drugs to their biological targets. Most commonly, mesoporous nanostructured silica, carbon nanotubes, gold, and iron oxide nanoparticles have been thoroughly studied in recent years. Opposite to polymeric and lipid nanostructured materials, inorganic nanomaterial drug carriers are unique because they have shown astonishing theranostic (therapy and diagnostics) effects, expressing an undeniable part of future use in medicine. This review summarizes research from development to the most recent discoveries in the field of nanostructured materials and their applications in drug delivery, including promising metal-based complexes, platinum, palladium, ruthenium, titanium, and tin, to tumor cells and possible use in theranostics. Full article

This retrospective cohort study evaluated characteristics, treatment patterns, and clinical outcomes in adults with locally advanced/metastatic urothelial carcinoma (la/mUC) receiving first-line (1L) systemic treatment with or without avelumab 1L maintenance (1LM) between January 2020 and July 2023. The index date was the first date with a claim for 1L systemic therapy after a la/mUC diagnosis. Patients with continuous health plan enrollment for ≥6 months before and ≥1 month after the index date were identified from Carelon Research’s Healthcare Integrated Research Database. Of 2820 patients receiving 1L treatment, 37.0% received platinum-based chemotherapy (PBC); 39.0%, immuno-oncology (IO) monotherapy; and 24.0%, other therapies. Renal disease and other comorbidities influenced 1L regimen choice. Healthcare resource utilization (HCRU) and costs were reported for patients receiving second-line (2L) treatment. HCRU was high in 32.8% of patients (926 of 2820) who received 2L treatment. Median all-cause direct medical costs per patient per month were USD 15,859, USD 19,781, USD 11,346, and USD 9516 for 1L PBC, 1L PBC + avelumab 1LM, 1L IO monotherapy, and 1L other therapies, respectively. Most direct healthcare costs were attributed to all-cause outpatient visits. Full article

Pleural malignancies represent a clinically devastating group of oncological disorders, most commonly arising from metastatic disease, with lung and breast cancers being the most frequent primary sites. Malignant pleural mesothelioma is a primary malignancy of the pleura and occurs less often than metastatic pleural disease. Pleural malignancies often present with malignant pleural effusion, which typically indicates advanced-stage disease and is associated with poor overall prognosis. Treatment of pleural malignancies includes both palliative and definitive approaches. Palliative interventions primarily aim to relieve symptoms and improve quality of life. Definitive treatments include systemic chemotherapy, targeted therapy, and immunotherapy, depending on the type and molecular profile of the underlying tumor. In mesothelioma, platinum-based chemotherapy in combination with pemetrexed remains the cornerstone of treatment, while the combination of nivolumab and ipilimumab is recommended as first-line therapy for unresectable disease. For metastatic disease, systemic therapy is typically tailored to the primary tumor’s characteristics. Intrapleural administration of chemotherapeutic agents is one of the therapeutic strategies and hyperthermic intrathoracic chemotherapy and pressurized intrathoracic aerosol chemotherapy are the most recent innovations that are under active investigation. This review provides an up-to-date synthesis of systemic chemotherapy strategies for pleural malignancies, their integration with targeted and immune-based therapies, and recent advances in intrapleural chemotherapy modalities. It also explores existing knowledge gaps and outlines directions for future research and potential changes in clinical practice. Full article

Background: Nedaplatin is a platinum-based anticancer drug that combines the benefits of Cisplatin and Carboplatin, retaining Cisplatin’s anticancer activity while reducing toxicity similar to Carboplatin. After hydrolysis, Nedaplatin targets purines in DNA and forms cross-links that induce cell death via apoptosis. However, it is important to consider how the presence of other chemical compounds with structural similarities to Adenine or Guanine, such as aromatic, purine, or pyrimidine compounds containing a nitrogen atom with a free electron pair, might influence its activity at the cellular level. Alkaloids with structures similar to DNA nucleobases are common, and their influence on Nedaplatin’s activity requires investigation. Methods: In this study, the interactions between Nedaplatin (including its hydrolyzed forms, such as [Pt(NH₃)₂(H₂O)₂]²⁺ and [Pt(NH₃)₂(H₂O)(OH)]⁺) and nucleobases (Adenine and Guanine) and purine alkaloids (Caffeine, Theobromine and Theophylline) were thoroughly investigated using theoretical (density functional theory, DFT) and experimental (UV-Vis spectroscopy) methods. DFT calculations were performed at the B3LYP/6-31G(d,p)/LANL2DZ and MN15/def2-TZVP levels, with structure optimization and harmonic analysis in the gas phase and aqueous solution (modeled using IEF-PCM). UV-Vis spectroscopy was used to verify theoretical findings by examining changes in absorption spectra. Results: Both theoretical and experimental studies confirmed that Nedaplatin forms complexes with both nucleobases and purine alkaloids. Nedaplatin was found to exhibit a higher affinity for nucleobases than for purine alkaloids. Furthermore, this affinity was dependent on the computational method used and on the hydrolyzed form of Nedaplatin. Theoretical calculations showed the formation of stable complexes through bonding with nitrogen atoms in the ligand molecules, which was confirmed by changes in UV-Vis spectra, indicating adduct formation. Conclusions: The results indicate that Nedaplatin readily forms complexes with both nucleobases and purine alkaloids, showing a stronger affinity for nucleobases. This finding highlights the potential importance of Nedaplatin’s interactions with other compounds present in the body, which may influence its effectiveness and mechanism of action in cancer therapy. These studies provide new insights into the molecular mechanisms of Nedaplatin’s action and may contribute to a better understanding of its pharmacological interactions. However, research requires confirmation not only in in vivo studies but also in clinical trials. Full article

Ovarian cancer is the most lethal gynecologic malignancy, which causes 313,959 new cases and 207,252 deaths worldwide annually. The lack of specific symptoms, together with no effective screening tools, results in 75% of patients receiving their diagnosis at an advanced stage. The combination of cytoreductive surgery with platinum-based chemotherapy plays a pivotal role in the treatment of advanced epithelial ovarian cancer, but patients still experience poor long-term survival because of frequent relapses and chemotherapy resistance. The treatment landscape has evolved because bevacizumab and Poly-ADP Ribose Polymerase inhibitors now serve as frontline and maintenance therapies for homologous recombination-deficient tumors. Treatment decisions for recurrent disease depend on platinum sensitivity assessment, which determines the appropriate therapeutic approach, while targeted agents deliver significant benefits to specific patient groups. The development of antibody-drug conjugates such as mirvetuximab soravtansine and immunotherapy, including checkpoint inhibitors and cancer vaccines, demonstrates promising investigative potential. The precision of therapy improves through the use of emerging biomarkers and molecular profiling techniques. The future management of this disease may change because of innovative approaches that include adoptive cell therapy, cytokine therapy, and oncolytic viruses. The progress made in ovarian cancer treatment still faces challenges when it comes to drug resistance, survival improvement, and life quality preservation. The development of translational research alongside clinical trials remains essential to bridge treatment gaps while creating personalized therapies based on molecular and clinical tumor characteristics. Full article

Background/Objectives: To summarize the relevant trials relating to novel strategies and therapeutic advances in the treatment of bladder cancer. Methods: A comprehensive review of the literature and recent/ongoing clinical trials was conducted, focusing on novel treatments and strategies for bladder cancer. Trials started or published as of 2020 were included. Results: The standard of care for MIBC remains neoadjuvant chemotherapy with perioperative immunotherapy in the cisplatin-eligible population, while guidelines do not exist for cisplatin-ineligible patients. Strategies under investigation include combinations of chemotherapy, immunotherapy, radiation, and/or novel therapies, such as ADCs, targeted agents, intravesical treatments, and personalized vaccines. Bladder-sparing approaches using these novel therapies are also being studied. In the advanced/metastatic setting, enfortumab vedotin plus pembrolizumab has supplanted platinum-based chemotherapy as the first-line treatment option. For those with contraindications, or who progress, strategies under investigation include newer immunotherapies and ADCs, novel small molecule inhibitors, and cellular therapies. Conclusions: The treatment landscape for bladder cancer has changed drastically within the last few years. Ongoing trials hope to build on this success by investigating bladder-sparing strategies for MIBC and novel systemic therapies in advanced patients. Full article

Ovarian cancer is the most lethal gynecological cancer. Up to 75% of cases are high-grade serous ovarian cancer (HGSOC) that have high chemosensitivity to first-line platinum-based therapies. However, 75% of patients will become chemoresistant following relapse. The underlying mechanism for developing resistance to chemotherapy in HGSOC is poorly understood. In this study, we employed Matrix-Assisted Laser Desorption/Ionization–Mass Spectrometry Imaging (MALDI-MSI) on matching formalin-fixed paraffin-embedded (FFPE) HGSOC tissues at the time of diagnosis and following relapse with chemotherapy-resistant disease (n = 4). We identified m/z values that were differentially abundant in the matching diagnosis and relapse HGSOC tissues. These were matched to proteins using nano-liquid chromatography tandem mass spectrometry (LC-MS/MS). We identified upregulated proteins in the HGSOC relapse tissues, including COL12A1, FUBP1, PLEC, SLC4A1, and TKT. These proteins were validated by immunohistochemistry (IHC) and gene expression using online databases. IHC showed COL12A1, FUBP1, PLEC, SLC4A1, and TKT protein abundance were significantly elevated in HGSOC relapse tissues compared to matching tissues at diagnosis. COL12A1, FUBP1, PLEC, and TKT mRNA expression levels were significantly increased in HGSOC compared to normal ovary and associated with poor prognosis in HGSOC. We confirmed that higher protein abundance of both COL12A1 and PLEC correlated with reduced progression-free survival in HGSOC patients. Furthermore, both COL12A1 and PLEC mRNA and protein levels were significantly associated with chemotherapy resistance. In summary, using MALDI-MSI, we have identified proteins, including COL12A1 and PLEC, associated with chemotherapy resistance to be further evaluated as HGSOC biomarkers and/or therapeutic targets. Full article