Search Results (2,916)

Hodgkin’s Lymphoma (HL) affects approximately 8500 individuals annually in the United States. The 5-year relative survival rate has improved to 88.5%, driven by transformative advances in immunotherapy and precision oncology. The integration of Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) has redefined treatment paradigms. The phase III SWOG S1826 trial established nivolumab plus doxorubicin, vinblastine, and dacarbazine (N + AVD) as an emerging new standard for advanced-stage HL, achieving a 2-year progression-free survival (PFS) of 92% compared to 83% for BV plus AVD (HR 0.48, 95% CI: 0.33–0.70), with superior safety, particularly in patients over 60. In relapsed/refractory HL, pembrolizumab outperforms BV, with a median PFS of 13.2 versus 8.3 months (HR 0.65, 95% CI: 0.48–0.88), as demonstrated in the KEYNOTE-204 trial. Emerging strategies, including novel ICI combinations, minimal residual disease (MRD) monitoring via circulating tumor DNA (ctDNA), and artificial intelligence (AI)-driven diagnostics, promise to further personalize therapy. This review synthesizes HL’s epidemiology, pathogenesis, diagnostic innovations, and therapeutic advances, highlighting the role of precision medicine in addressing unmet needs and disparities in HL care. Full article

Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article

Background: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy arising from the nasopharyngeal mucosa. Despite treatment advances such as the use of intensity-modulated radiotherapy and immune checkpoint inhibitors, resistance remains a significant clinical challenge. Many tumours are also diagnosed at an advanced stage associated with poor prognosis. Objective: This review aims to explore the biological roles of autophagy in NPC, primarily highlighting its involvement in disease pathogenesis and treatment resistance. Methods: We performed a review of the recent literature examining the role of autophagy-related pathways in NPC pathogenesis, biomarker discovery, and therapeutic targeting. Results: Autophagy plays a dual role in NPC as it contributes to both tumour suppression and progression. It is involved in tumour initiation, metastasis, immune modulation, and treatment resistance. Autophagy-related genes such as SQSTM1, Beclin-1, and AURKA may serve as prognostic and therapeutic biomarkers. Various strategies are being investigated for their role to modulate autophagy using pharmacologic inhibitors, RNA interventions, and natural compounds. Conclusions: Further research into autophagy’s context-dependent roles in NPC may inform the development of personalised therapies and allow progress in translational and precision oncology. Full article

Chemotherapy remains a cornerstone in the treatment of esophageal cancer (EC), yet chemoresistance remains a critical challenge, leading to poor outcomes and limited therapeutic success. Mitochondrial DNA (mtDNA) has emerged as a pivotal player in mediating these responses, influencing cellular metabolism, oxidative stress regulation, and apoptotic pathways. This review provides a comprehensive overview of the mechanisms by which mtDNA alterations, including mutations and copy number variations, drive chemoresistance in EC. Specific focus is given to the role of mtDNA in metabolic reprogramming, including its contribution to the Warburg effect and lipid metabolism, as well as its impact on epithelial–mesenchymal transition (EMT) and mitochondrial bioenergetics. Recent advances in targeting mitochondrial pathways through novel therapeutic agents, such as metformin and mitoquinone, and innovative approaches like CRISPR/Cas9 gene editing, are also discussed. These interventions highlight the potential for overcoming chemoresistance and improving patient outcomes. By integrating mitochondrial diagnostics with personalized treatment strategies, we propose a roadmap for future research that bridges basic mitochondrial biology with translational applications in oncology. The insights offered in this review emphasize the critical need for continued exploration of mtDNA-targeted therapies to address the unmet needs in EC management and other diseases associated with mitochondria. Full article

Background/Objectives: Pulmonary typical carcinoid (TC) is a rare type of primary neuroendocrine neoplasm of the lung with indolent behavior and a good prognosis. The main treatment strategy is surgery, the extent of which is controversial given the nature of the disease. The aim of this study is to assess whether the extent of resection influences survival and recurrence in patients undergoing lung resection and lymphadenectomy for TC and to investigate negative prognostic factors for OS. Methods: A single-centre retrospective study of 15 years’ experience was conducted. Data from all patients who underwent lung resection and lymphadenectomy for TC were collected. Patients were divided into two groups: anatomical and non-anatomical resections. Perioperative and long-term oncological results were analyzed. Results: In total, 115 patients were surgically treated for TC, of whom 83 (72%) underwent anatomical resection and 32 (28%) non-anatomical resection. Univariate analyses showed that age, left lower lobe, and many comorbidities had a detrimental effect on OS, whereas on multivariate analysis, only left lower lobe location and a high Charlson–Deyo comorbidity index (CCI) were confirmed as negative prognostic factors for OS. At a median follow-up of 93 months (IQR 57-129), the OS survival curves show a slightly lower trend for non-anatomical resections (p 0.152), while no differences were found for DFS. Conclusions: The results of this study confirm that in selected patients at risk for major resections, non-anatomical resection can be used to treat TC when R0 is achievable. These data, together with evidence from the literature, highlight the importance of patient-centred care in this rare disease. Full article

Background: Childhood cancer is considered one of the main causes of mortality and morbidity worldwide. There is strong evidence of the oral toxic effects of oncologic treatments, but their incidence is difficult to determine. The novel therapeutic strategies in Pediatric Oncology have led to increased survival in this population, resulting in an increased incidence of long-term effects, which diminish the patient’s quality of life. Methods: The search for articles started on 5 November 2024 and ended on 5 December 2024. Following the PRISMA Statement, a total of 1266 articles were obtained, from which 13 were selected for review. All articles were considered to be of high quality. The antineoplastic treatments used in them were chemotherapy, radiotherapy, surgery and immune therapy. Results: Most articles were cohorts and case controls. Only one case report was obtained. The results revealed that the most prevalent sequelae in the pediatric population after antineoplastic treatment were enamel alterations, microdontia, dental caries, periodontal disease, gingivitis, hyposalivation, alteration of the oral microbiome, alteration of mandibular bone density and malocclusion. The lesions are different depending on the therapy used. Conclusions: Oncologic treatments in children with cancer cause multiple oral sequelae such as microdontia, dental caries, enamel alterations, salivary gland alterations, mucositis and root resorption. It cannot be concluded which therapy has the most detrimental effect as each has a different mechanism of action in the oral cavity. Full article

Background/Objectives: Phase II oncology trials often rely on single-arm designs to test $H_0:\pi ={\pi }_0$ versus $H_a:\pi >{\pi }_0$, especially when randomized trials are infeasible due to cost or disease rarity. Traditional approaches, such as the exact binomial test and Simon’s two-stage design, tend to be conservative, with actual Type I error rates falling below the nominal $\alpha$ due to the discreteness of the underlying binomial distribution. This study aims to develop a more efficient and flexible method that maintains accurate Type I error control in such settings. Methods: We propose a convolution-based method that combines the binomial distribution with a simulated normal variable to construct an unbiased estimator of $\pi$. This method is designed to precisely control the Type I error rate while enabling more efficient trial designs. We derive its theoretical properties and assess its performance against traditional exact tests in both one-stage and two-stage trial designs. Results: The proposed method results in more efficient designs with reduced sample sizes compared to standard approaches, without compromising the control of Type I error rates. We introduce a new two-stage design incorporating interim futility analysis and compare it with Simon’s design. Simulations and real-world examples demonstrate that the proposed approach can significantly lower trial cost and duration. Conclusions: This convolution-based approach offers a flexible and efficient alternative to traditional methods for early-phase oncology trial design. It addresses the conservativeness of existing designs and provides practical benefits in terms of resource use and study timelines. Full article

Background: Pleural mesothelioma (PM) is a type of cancer that is difficult to diagnose and treat. Patients may have vastly varying prognoses, and prognostic factors may help guide the clinical approach. As a recently identified biomarker, the pan-Immune-Inflammation-Value (PIV) is a simple, comprehensive, and peripheral blood cell-based biomarker. Methods: The present study represents a retrospective observational analysis carried out within a single-center setting. Ninety-five patients with PM stages I–IV were enrolled in the study. We analyzed the correlation between patients’ demographic characteristics, clinicopathological factors such as histological subtypes, surgery status, tumor thickness, blood-based parameters, and treatment options with their prognoses. PIV was calculated by the following formula: (neutrophil count × monocyte count × platelet count)/lymphocyte count. Additionally, blood-based parameters were used to calculate the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII). Results: We categorized the patients into two groups, low PIV group (PIV ≤ 732.3) and high PIV group (PIV > 732.3) according to the determined cut-off value, which was defined as the median. It was revealed that high PIV was associated with poor survival outcomes. The median follow-up period was 15.8 months (interquartile range, IQR, 7.1 to 29.8 months). The median overall survival (OS) was significantly longer in patients in the low PIV group (median 29.8 months, 95% confidence interval (CI), 15.6 to 44) than the high PIV group (median 14.7 months, 95% CI, 10.8 to 18.6 p < 0.001). Furthermore, the study revealed that patients with low PIV, NLR, and SII values were more likely to be eligible for surgery and were diagnosed at earlier stages. Additionally, these markers were identified as potential predictors of disease-free survival (DFS) in the surgical cohort and of treatment response across the entire patient population. Conclusions: In addition to well-established clinical factors such as stage, histologic subtype, resectability, and Eastern Cooperative Oncology Group (ECOG) performance status (PS), PIV emerged as an independent and significant prognostic factor of overall survival (OS) in patients with PM. Moreover, PIV also demonstrated a remarkable independent prognostic value for disease-free survival (DFS) in this patient population. Additionally, some clues are provided for conditions such as treatment responses, staging, and suitability for surgery. As such, in this cohort, it has outperformed the other blood-based markers based on our findings. Given its ease of calculation and cost-effectiveness, PIV represents a promising and practical prognostic tool in the clinical management of pleural mesothelioma. It can be easily calculated using routinely available laboratory parameters for every cancer patient, requiring no additional cost or complex procedures, thus facilitating its integration into everyday clinical practice. Full article

Background/Objectives: Nonoperative management (NOM) of patients with locally advanced rectal cancer (LARC) who achieve a complete clinical response (cCR) to total neoadjuvant therapy (TNT) has been shown to be oncologically safe and is an attractive treatment option for patients. However, identifying responders to TNT that may benefit from nonoperative management is clinically challenging. Circulating tumor DNA (ctDNA) testing has shown promise in detecting minimal residual disease but has not yet been studied extensively within this clinical context. Methods: This is a single-institution retrospective case series study of LARC patients treated with TNT from 2019 to 2023 who underwent ctDNA testing as an adjunct to standard clinical response assessments. Results: A total of 28 patients had ctDNA testing as part of their response assessments after TNT. In total, 9 patients had positive ctDNA, and 19 patients had negative ctDNA during surveillance. Baseline characteristics of these two groups were not different. In this study, 6/9 (67%) patients who had positive ctDNA required surgery for residual rectal cancer, whereas only 4/19 (21%) patients who had negative ctDNA required surgery (p = 0.035). Conclusions: ctDNA testing has the potential to detect MRD in LARC patients treated with TNT. Full article

Background/Objectives: Preoperative strategies for hepatocellular carcinoma (HCC) requiring major hepatectomy remain controversial, particularly in “borderline resectable” cases. This study aimed to evaluate the oncological benefit and perioperative safety of Yttrium-90 transarterial radioembolization (TARE) in patients undergoing right or extended right hepatectomy for HCC. Material and Methods: All consecutive patients who underwent right or extended right hepatectomy for HCC at a single tertiary center between January 2013 and December 2023 were retrospectively reviewed. Patients were grouped based on whether they received preoperative TARE or underwent upfront resection. Outcomes analyzed included perioperative morbidity and long-term oncological endpoints. Results: A total of 39 patients were included, of whom 18 received preoperative TARE and 21 underwent upfront surgery. Patients in the TARE group showed significantly greater tumor necrosis at pathology (70% vs. 10%, p = 0.002) and more frequent extended resections. Five-year cancer-specific survival (80.4% vs. 33.5%, p = 0.011), recurrence-free survival (33.8% vs. 14.0%, p = 0.047), and curative-intent disease-free survival (69.3% vs. 18.9%, p = 0.0037) were significantly higher in the TARE group. Overall survival showed a favorable trend. Intraoperative outcomes, postoperative morbidity, and 90-day mortality were comparable between groups. Conclusions: Preoperative TARE is a safe and effective neoadjuvant strategy in selected patients with HCC undergoing major hepatectomy. It may enhance long-term oncological outcomes without increasing surgical risk, supporting its potential role in the management of borderline resectable HCC. Full article

Background: Statins exhibit pleiotropic anti-inflammatory, antioxidant, and immunomodulatory effects, suggesting their potential in non-cardiovascular conditions. However, evidence supporting their repurposing remains limited, and off-label prescribing policies vary globally. Objective: To systematically review evidence on statin repurposing in oncology and infectious diseases, and to assess Hungarian regulatory practices regarding off-label statin use. Methods: A systematic literature search (PubMed, Web of Science, Scopus, ScienceDirect; 2010–May 2025) was conducted using the terms “drug repositioning” OR “off-label prescription” AND “statin” NOT “cardiovascular,” following PRISMA guidelines. Hungarian off-label usage data from the NNGYK (2008–2025) were also analyzed. Results: Out of 205 publications, 12 met the inclusion criteria—75% were oncology-focused, and 25% focused on infectious diseases. Most were preclinical (58%); only 25% offered strong clinical evidence. Applications included hematologic malignancies, solid tumors, Cryptococcus neoformans, SARS-CoV-2, and dengue virus. Mechanisms involved mevalonate pathway inhibition and modulation of host immune responses. Hungarian data revealed five approved off-label statin uses—three dermatologic and two pediatric metabolic—supported by the literature and requiring post-treatment reporting. Conclusions: While preclinical findings are promising, clinical validation of off-label statin use remains limited. Statins should be continued in cancer patients with cardiovascular indications, but initiation for other purposes should be trial-based. Future directions include biomarker-based personalization, regulatory harmonization, and cost-effectiveness studies. Full article

Lung cancer is one of the most common cancers and the leading cause of cancer-related death worldwide. Despite advancements, the overall survival rate for lung cancer remains between 10% and 20% in most countries. However, recent progress in diagnostic tools and therapeutic strategies has led to meaningful improvements in survival outcomes, highlighting the growing importance of personalized management based on accurate disease assessment. ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has become essential in the management of lung cancer, serving as a key imaging modality for initial diagnosis, staging, treatment response assessment, and follow-up evaluation. Recent developments in radiomics and artificial intelligence (AI), including machine learning and deep learning, have revolutionized the analysis of complex imaging data, enhancing the diagnostic and predictive capabilities of FDG PET/CT in lung cancer. However, the limitations of FDG, including its low specificity for malignancy, have driven the development of novel oncologic radiotracers. One such target is fibroblast activation protein (FAP), a type II transmembrane glycoprotein that is overexpressed in activated cancer-associated fibroblasts within the tumor microenvironment of various epithelial cancers. As a result, FAP-targeted radiopharmaceuticals represent a novel theranostic approach, offering the potential to integrate PET imaging with radioligand therapy (RLT). In this review, we provide a comprehensive overview of FDG PET/CT in lung cancer, along with recent advances in AI. Additionally, we discuss FAP-targeted radiopharmaceuticals for PET imaging and their potential application in RLT for the personalized management of lung cancer. Full article

Organoid and spheroid technologies have rapidly become pivotal in thyroid cancer research, offering models that are more physiologically relevant than traditional two-dimensional culture. In the study of papillary and anaplastic thyroid carcinomas, two subtypes that differ both histologically and clinically, three-dimensional (3D) models offer unparalleled insights into tumor biology, therapeutic vulnerabilities, and resistance mechanisms. These models maintain essential tumor characteristics such as cellular diversity, spatial structure, and interactions with the microenvironment, making them extremely valuable for disease modeling and drug testing. This review emphasizes recent progress in the development and use of thyroid cancer organoids and spheroids, focusing on their role in replicating disease features, evaluating targeted therapies, and investigating epithelial–mesenchymal transition (EMT), cancer stem cell behavior, and treatment resistance. Patient-derived organoids have shown potential in capturing individualized drug responses, supporting precision oncology strategies for both differentiated and aggressive subtypes. Additionally, new platforms, such as thyroid organoid-on-a-chip systems, provide dynamic, high-fidelity models for functional studies and assessments of endocrine disruption. Despite ongoing challenges, such as standardization, limited inclusion of immune and stromal components, and culture reproducibility, advancements in microfluidics, biomaterials, and machine learning have enhanced the clinical and translational potential of these systems. Organoids and spheroids are expected to become essential in the future of thyroid cancer research, particularly in bridging the gap between laboratory discoveries and patient-focused therapies. Full article

Background: Lung cancer remains one of the leading causes of cancer-related mortality worldwide. While most diagnoses occur in outpatient settings, a subset of cases are incidentally identified during emergency department (ED) visits. The clinical characteristics and treatment decisions of these patients, particularly in relation to social background factors such as living situation and access to primary care, remain poorly understood. Methods: We conducted a retrospective study of patients diagnosed with malignancies in the ED of a single institution between April 2018 and December 2021. Patients diagnosed with lung cancer within 60 days of an ED visit were included. Data on demographics, disease status, treatment decisions, and background factors—including whether patients lived alone or had a primary care physician (PCP)—were extracted and analyzed. Results: Among 32,108 patients who visited the ED, 148 were diagnosed with malignancy within 60 days; 23 had lung cancer. Of these, 69.6% had metastatic disease at diagnosis, and 60.9% received active treatment (surgery or chemotherapy). No significant associations were observed between the extent of disease and either living arrangement or PCP status. However, the presence of a PCP was significantly associated with the selection of best supportive care (p = 0.023). No significant difference in treatment decisions was observed based on age (cutoff: 75 years). Conclusions: Although social background factors such as living alone were not significantly associated with cancer stage or treatment choice, the presence of a primary care physician was associated with a higher likelihood of best supportive care being selected. This may indicate that patients with an established PCP have more clearly defined care goals at the end of life. These findings suggest that primary care access may play a role in shaping end-of-life care preferences, highlighting the importance of personalized approaches in acute oncology care. Full article

Background/Objectives: This study aimed to assess real-world toxicity and efficacy data of patients with early and advanced breast cancer (BC) who received treatment with abemaciclib. Methods: This was a prospective/retrospective multi-institutional collection of clinicopathological, toxicity, and outcome data from patients with early or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative BC who received treatment with abemaciclib in combination with endocrine therapy in departments of oncology in Greece. Treatment combinations of abemaciclib with any endocrine therapy were accepted. The primary end point was toxicity rate in all patients of the study. Results: From June/2021 to May/2024, 245 women received abemaciclib/endocrine combination therapy; the median age was 57 years. Of these, 169 (69%) received abemaciclib as adjuvant therapy for early-stage disease, while 76 (31%) were treated for advanced BC. At the time of the data cutoff, 133 (84.7%) patients remained in the 2-year treatment period. The most common adverse event (AE) was diarrhea (51%), primarily Grade ≤ 2. Dose modifications due to AEs were required in 19.2% of cases, while treatment discontinuation occurred in 5.1%. There was no difference in dose modification/discontinuation rates between older patients (>65 years) and the remaining patients. For early-stage BC patients, the 2-year DFS and OS rates were 90.8% and 100%, respectively. In patients with advanced cancer (70, 30.8%), 1-year PFS and OS rates were 78% and 96.3%, respectively. Conclusions: This study confirms the safety and effectiveness of abemaciclib in alignment with registrational trials offering valuable insights into toxicity management and clinical outcomes in routine practice without identifying new safety concerns. Clinical Trial Registration: ClinicalTrials.gov NCT04985058. Full article