Search Results (210)

Introduction: Current treatments for patients with stage III non-small-cell lung cancer (NSCLC) are not sufficiently personalized, resulting in suboptimal outcomes and high mortality rates. The Developing Circulating and Imaging Biomarkers Towards Personalized Radiotherapy in Lung Cancer (VIGILANCE) study employs innovative health technologies to collect a range of clinical data and features. This includes longitudinal analyses of cell-free and circulating tumor DNA from blood samples and radiomic features extracted from standard-of-care imaging. Additionally, patient-reported outcome measures will be collected to capture patients’ symptoms and quality of life. This will provide invaluable insight into the patient experience during and after radiotherapy. We aim to evaluate whether the data, including patient-reported outcomes, can serve as biomarkers to refine treatment strategies, improve post-treatment follow-up and provide patients with realistic outcome predictions. Key endpoints include the following: (1) assessing whether baseline ctDNA status and its early on-treatment dynamics can identify patients with radioresistant disease who could benefit from treatment intensification; (2) determining whether post-radiotherapy ctDNA clearance can predict benefit from consolidation durvalumab, potentially sparing ctDNA-negative patients from unnecessary immunotherapy; and (3) developing integrated models combining novel ctDNA and radiomic biomarkers to distinguish between radiation fibrosis and tumor recurrence and to predict survival. We adopt a pragmatic approach by recruiting patients receiving standard-of-care treatments in a real-world setting. In addition, most of the clinical data is already routinely collected in our center, except for the blood tests for cell-free and circulating tumor DNA analysis. Methods and analysis: This is a single-center, prospective, exploratory, longitudinal, follow-up study, recruiting patients with stage III NSCLC undergoing standard-of-care curative-intent radiotherapy (with or without systemic therapy). Data collection spans from baseline to during radiotherapy and is extended up to 1 year following radiotherapy. The longitudinal analysis aims to describe and characterize dynamic changes in the collected features and assess their utility as prognostic and response biomarkers. Trial registration number: NCT06086574. Full article

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality, with therapeutic resistance posing the primary barrier to durable outcomes. Beyond genetic and epigenetic alterations, amino acid transporter-driven metabolic reprogramming—mediated by LAT1 (SLC7A5), ASCT2 (SLC1A5), and xCT (SLC7A11)—supports tumor proliferation, redox homeostasis, and immune escape. Their preferential expression in NSCLC highlights their potential as therapeutic targets and predictive biomarkers. In parallel, α-particle therapy has gained attention for its capacity to eradicate resistant clones through densely clustered, irreparable DNA double-strand breaks. Astatine-211 (²¹¹At) combines a clinically relevant half-life, high linear energy transfer, and predictable decay scheme, positioning it as a unique candidate among α-emitters. Preclinical studies of ²¹¹At-labeled transporter ligands, particularly LAT1-targeted conjugates, demonstrate potent tumor suppression and synergy with targeted therapy, chemotherapy, radiotherapy, immunotherapy, and ferroptosis inducers. Advances in radiochemistry, delivery systems (antibodies, peptides, and nanocarriers), and PET tracers such as [¹⁸F]FAMT and [¹⁸F]FSPG collectively support a theranostic framework for patient stratification and adaptive dosing. By linking transporter biology with α-particle delivery, ²¹¹At-based theranostics offer a mechanistically orthogonal strategy to overcome resistance and heterogeneity in NSCLC. Successful translation will depend on precise dosimetry, scaffold stabilization, and biomarker-guided trial design, enabling progression toward first-in-human studies and future integration into multimodal NSCLC therapy. Full article

Stereotactic ablative radiotherapy (SABR) has revolutionized the management of patients with oligometastatic and selected primary cancers due to its ability to deliver highly conformal, high-dose radiation in few fractions with minimal toxicity. However, the biological heterogeneity among patients treated with SABR results in variable outcomes, emphasizing the need for predictive and prognostic biomarkers to guide patient selection and post-treatment management. This narrative review discusses the current landscape of biomarker development in the context of SABR across tumor types. Key classes include circulating tumor DNA (ctDNA), extracellular vesicles (EVs), radiomic features, and immunological markers. We highlight the role of each biomarker category in refining therapeutic approaches, their integration into ongoing clinical trials, and future directions for personalized SABR paradigms. Translating these promising biomarker strategies into clinical SABR workflows will require further standardisation, validation, and regulatory alignment. Full article

Objectives: This study evaluated the utility of complex morphometric analyses for predicting radiation pneumonitis (RP) and proposed a quantitative prognostic framework for patients with non-small cell lung cancer (NSCLC) undergoing curative-intent radiotherapy (RT). Imaging biomarkers, including box-counting fractal dimension (BoxFD), lacunarity, and minimum spanning tree fractal dimension (MSTFD), were assessed for their prognostic significance. Materials and Methods: We retrospectively analyzed 166 NSCLC patients who received curative-intent RT and had both pre-treatment and follow-up chest CT scans. Among them, 85 received RT alone and 81 underwent concurrent chemoradiotherapy (CCRT). Fractal features were measured to build a Random Forest model (RFM) predicting RP of grade ≥ 2, and the most important features were used to construct a decision tree model. Results: RP of grade ≥ 2 occurred in 19 patients (22.3%) in the RT alone group and 44 patients (54.3%) in the CCRT group. Lacunarity increased significantly post-RT in both groups, while BoxFD and MSTFD showed no significant changes. In the RFM, pre-RT MSTFD and lung dose parameters (V10 in RT alone; V5–V20 in CCRT) were identified as key predictors. Decision tree models based on these features achieved high predictive performance, with AUROC of 0.83 and 0.85, and F1 scores of 0.92 and 0.76 for RT alone and CCRT groups, respectively. Conclusions: Fractal imaging biomarkers demonstrated promising prognostic value for predicting grade ≥ 2 RP in NSCLC patients. The proposed decision tree model may serve as a practical tool for early identification of high-risk patients, facilitating personalized treatment strategies and informing future research. Full article

Cancer remains a major global health burden, representing one of the leading causes of mortality among noncommunicable diseases worldwide. Although conventional treatment modalities, including surgical resection, chemotherapy, radiotherapy, targeted therapy, and immunotherapeutic interventions, have demonstrated clinical benefits, their therapeutic efficacy is often constrained by inherent limitations such as low specificity, systemic toxicity, or tumor heterogeneity. These challenges underscore the imperative for developing innovative treatment strategies. Emerging evidence has implicated ion channels as critical players in oncogenesis and cancer progression. These proteins modulate diverse oncogenic phenotypes, including uncontrolled proliferation, metastatic dissemination, and apoptotic resistance. Their frequent dysregulation in malignancies correlates with disease aggressiveness and clinical outcomes, positioning them as promising targets for precision oncology. Notably, pharmacological modulation of ion channels exerts multifaceted antitumor effects, with several channel-targeting agents advancing through clinical trials. This review explores recent advances in ion channel-targeted therapies, emphasizing their mechanisms, clinical applications, and challenges. Furthermore, we examine the pathophysiological contributions of ion channels to tumor biology and evaluate their emerging utility as predictive biomarkers, providing perspectives on addressing critical gaps in current oncologic management. Full article

Small Cell Lung Cancer (SCLC) is an aggressive neuroendocrine malignancy representing approximately 15% of all lung cancers. Characterized by rapid progression, early metastasis, and high circulating tumor cell burden, SCLC has a poor prognosis. Although initial responses to chemotherapy, radiotherapy, and immunotherapy are common, relapse due to acquired resistance is nearly inevitable. Molecular studies have identified four transcription factor–driven subtypes—ASCL1, NEUROD1, POU2F3, and YAP1—each with distinct biological traits and therapeutic vulnerabilities. However, clinical classification remains largely homogeneous, limiting precision treatment strategies. Immunotherapy has modestly improved survival, as demonstrated in trials like IMpower133, CASPIAN, and ADRIATIC. Yet only a small subset of patients—approximately 12%—achieve long-term survival beyond five years. Understanding the biological and immunological profiles of these exceptional responders is critical. Future research should prioritize comprehensive biomarker integration, including PD-L1, TMB, DLL3, CD3, and emerging targets. Novel agents such as tarlatamab (DLL3-targeting) and ifinatamab deruxtecan (B7-H3–targeting) have shown encouraging efficacy in early-phase trials, though predictive markers remain elusive. A multi-dimensional approach combining tissue, blood, and immune profiling is essential to advance precision oncology in SCLC and improve patient selection for emerging therapies. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a 5-year overall survival below 12% and high recurrence rates even after R0 resection. Traditionally managed with a “surgery-first” approach, two consistent observations—the near-universal presence of micrometastatic disease at diagnosis and the frequent inability to complete adjuvant therapy—have driven the integration of neoadjuvant therapy (NAT) into clinical practice. NAT offers several theoretical and practical advantages: early systemic control of occult disease, improved delivery and completion of multimodal treatment, biological selection of surgical candidates, and increased R0 resection rates. While in borderline resectable PDAC, randomized trials have consistently demonstrated improved margin-negative resection rates and early survival benefits compared with upfront surgery, in resectable PDAC, evidence is more heterogeneous. Real-world studies corroborate trial findings, reporting higher R0 rates and reduced lymph node positivity without increased perioperative risk, but also highlight substantial heterogeneity in regimens, duration, and radiotherapy use. Limitations to universal NAT adoption include reliance on anatomy-based resectability criteria, absence of validated predictive biomarkers, challenges in response assessment, and concerns over disease progression during preoperative treatment. Future developments will focus on integrating molecular profiling, circulating tumor DNA dynamics, and advanced imaging into patient selection and treatment adaptation, supported by biomarker-enriched and adaptive trial designs. NAT is thus evolving from a selective strategy for borderline disease to an innovative framework to optimize multimodal treatment delivery and refine patient selection in PDAC, with the potential to improve surgical outcomes and inform systemic therapy decisions in both resectable and borderline resectable settings Full article

Background: Rectal cancer is common and frequently treated with neoadjuvant radiotherapy prior to surgery to reduce the risk of tumour recurrence. However, the therapeutic benefits and side effects of radiotherapy can vary between patients, and there are currently no validated biomarkers to predict treatment response. Tumour cell density (TCD) and tumour-infiltrating lymphocyte (TIL) density are proven prognostic biomarkers in colorectal cancer; however, their utility in predicting radiotherapy response remains unclear. We assessed the prognostic and predictive value of TCD and TIL density in rectal cancer patients treated with radiotherapy. Methods: TCD was quantified using a manual point-counting method in 253 pre-treatment biopsies and across the entire tumour area of 569 resection specimens from the MRC CR07 clinical trial, which randomised patients to either neoadjuvant short-course radiotherapy (SCRT) or straight to surgery (control). TIL density was measured in 102 biopsies and matched resection specimens (73 SCRT, 29 control) across different tumour areas using deep learning-based cell detection in MIM (HeteroGenius Ltd., Leeds, UK). Cutoffs for low/high-TCD and TIL density were both pre-defined and derived from survival data using the survminer R package. Survival analyses were performed to evaluate the predictive and prognostic value of TCD/TIL in relation to overall and cancer-specific survival. Results: TCD in the resection specimens was lower in the SCRT group (19.9%, IQR 12.9–26.7%) than the control group (34.3%, IQR 27.7–40.5%, p < 0.001). In control resections, low-TCD was associated with a higher risk of all-cause mortality (HR 2.20, 95% CI 1.41–3.44, p < 0.001) and cancer-related death (HR 2.69, 95% CI 1.41–5.13, p = 0.0026). In contrast, after SCRT, low resection TCD was associated with a reduced risk of death (HR 0.63, 95% CI 0.40–0.98, p = 0.04). In the SCRT group, low biopsy TCD prior to radiotherapy was associated with a reduced risk of cancer-related death (HR 0.34, 95% CI 0.13–0.89, p = 0.028). Across both trial arms, TIL density was higher in pre-treatment biopsies than resections (2492 vs. 1304/mm², p < 0.001). Low biopsy TIL density was associated with an increased risk of all-cause mortality (HR 2.43, 95% CI 1.24–4.76, p = 0.01). The SCRT group had lower TIL density in the resection compared with controls (1210 vs. 1615/mm², p < 0.001), and low resection TIL density across the whole tumour area was associated with a higher risk of death (HR 2.55, 95% CI 1.11–5.87, p = 0.027). Conclusions: Our findings support the role of TCD and TIL density as quantitative biomarkers in rectal cancer patients. TCD can be used to assess the degree of response to radiotherapy, and contrasting survival associations are observed between straight-to-surgery and SCRT-treated patients. This study raises the possibility of using TCD as both a prognostic and predictive biomarker. TIL density failed to show predictive value but demonstrated expected prognostic associations. Full article

Purpose: This systematic review aims to analyze the literature on the application of AI in predicting patient outcomes and treatment-related toxicity in those undergoing SBRT or SRS across heterogeneous tumor sites. Materials and methods: Our review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, EMBASE and Scopus were systematically searched for English-language human studies evaluating AI for outcome and toxicity prediction in patients undergoing SBRT or SRS for solid tumors. Search terms included (“Stereotactic Body Radiotherapy” OR “SBRT” OR “Stereotactic Radiosurgery” OR “SRS” OR “Stereotactic Ablative Radiotherapy” OR “SABR”) AND (“Artificial Intelligence” OR “AI” OR “Machine Learning” OR “Deep Learning” OR “Radiomics”) AND (“Response Prediction” OR “Response to Treatment” OR “Outcome Prediction”) AND (“Toxicity” OR “Side Effects” OR “Treatment Toxicities” OR “Adverse Events”). Results: The search yielded 29 eligible retrospective studies, published between 2020 and 2025. Eight studies addressed early-stage primary lung cancer, highlighting the potential of AI-based models in predicting radiation-induced pneumonitis, fibrosis and local control. Five studies investigated AI models for predicting hepatobiliary toxicity following SBRT for liver tumors. Sixteen studies involved SRS-treated patients with brain metastases or benign intracranial neoplasms (e.g., arteriovenous malformations, vestibular schwannomas, meningiomas), exploring AI algorithms for predicting treatment response and radiation-induced changes. In the results, AI might have been exploited to both reaffirm already known clinical predictors and to identify novel imaging, dosimetric or biological biomarkers. Examples include predicting radiation pneumonitis in lung cancer, residual liver function in hepatic tumors and local recurrence in brain metastases, thus supporting tailored treatment decisions. Conclusions: Combining AI with SBRT could greatly enhance personalized cancer care by predicting patient-specific outcomes and toxicity. AI models analyze complex datasets, including imaging and clinical data, to identify patterns that traditional methods may miss, thus enabling more accurate risk stratification and reducing variability in treatment planning. With further research and clinical validation, this integration could make radiotherapy safer, more effective and contribute to advancement in precision oncology. Full article

Background: Stereotactic ablative radiotherapy (SABR) is increasingly used in the treatment of localized and metastatic renal cell carcinoma (RCC), a malignancy traditionally considered radioresistant. Beyond direct cytotoxicity, SABR may promote immunogenic cell death and modulate the tumor immune microenvironment, though the underlying mechanisms remain incompletely understood. Objectives and Methods: This study examined the immunomodulatory effects of two high-dose irradiation regimens (8 Gy and 3 × 8 Gy) in an in vitro model using two RCC cell lines (ACHN, Caki-2) and peripheral blood mononuclear cells (PBMCs) from healthy donors. Results: The 3 × 8 Gy regimen more effectively reduced tumor cell viability and proliferation, particularly in ACHN cells, suggesting differential radiosensitivity. Both regimens induced secretion of IL-6, IL-8, TGF-β, and VEGF, with levels varying by cell line and dose. Caki-2 cells exhibited a cytokine profile consistent with a pro-inflammatory and potentially immunosuppressive phenotype. Conditioned media from irradiated cells were used to stimulate PBMCs, revealing divergent responses. Media from 3 × 8 Gy-irradiated ACHN cells enhanced PBMC proliferation and increased CD8⁺ T cells and CD11c⁺ monocytes, along with IFN-γ, IL-2, and TNF-α secretion, suggesting immunostimulatory effects. Conversely, media from Caki-2 cells had minimal impact on PBMC proliferation and increased TGF-β levels. Conclusions: These results indicate that high-dose irradiation can differentially modulate immune responses in RCC cell lines, depending on tumor intrinsic properties and irradiation regimen. Further in vivo studies are warranted to validate these findings and support development of SABR immunotherapy combinations guided by predictive immune biomarkers. Full article

Background: Circulating tumor DNA (ctDNA), shed into bodily fluids by cancer cells through apoptosis, necrosis, or active secretion, is currently used in the field of genomic investigation in clinical settings, primarily for advanced stages of non-small-cell lung cancer (NSCLC). However, its potential role in guiding the multi-omic approach to early-stage NSCLC is emerging as a promising area of investigation. Efforts are being made to integrate the genomics not only in surgery, but also in the definition of long-term prognosis after surgical or radiotherapy and for the prediction of recurrence. Methods: An extensive literature search was conducted on PubMed, covering publications from 2000 to 2024. Using the advanced search tool, titles and abstracts were filtered based on the following keywords: ctDNA, early stage, NSCLC. From this search, 20 studies that fulfilled all inclusion criteria were selected for analysis in this review. Results: This review highlights the growing body of evidence supporting the potential clinical use of ctDNA as a genomic biomarker in managing early-stage NSCLC. Baseline ctDNA levels offer valuable information about tumor molecular biology and histological characteristics. Beyond its prognostic value before treatment, liquid biopsy has proven useful for tracking minimal residual disease and forecasting recurrence following curative interventions such as surgery or radiotherapy. Future adjuvant treatment decisions may increasingly rely on predictive models that incorporate liquid biopsy findings alongside other clinical factors. Conclusions: The potential use of this analyte introduces new opportunities for the integration of genomic data in treatment, as well as relapse monitoring with more accurate and innovative than traditional methods, particularly in patients with early-stage NSCLC Full article

Gastric cancer remains a significant global health challenge, with regional and demographic disparities in incidence, mortality, and treatment outcomes. Despite advances in screening and early detection, prognosis remains poor for many patients, particularly those with advanced disease. Recent insights into DNA damage response pathways have uncovered critical molecular vulnerabilities in gastric tumors, including frequent TP53 mutations, ARID1A loss, ATM deficiency, and oncogene-driven replication stress, which render these cancers highly dependent on the ATR–CHK1 axis for survival. This review synthesizes current clinical and preclinical evidence on ATR and CHK1 inhibitors as therapeutic strategies in gastric cancer. Emphasis is placed on synthetic lethality, immune modulation, and the potential for combination regimens with chemotherapy, radiotherapy, or immune checkpoint blockade. Mechanisms of resistance, including transcription-associated replication stress modulation and bypass signaling networks, are discussed, alongside strategies to predict and overcome therapeutic failure. The review also highlights the importance of biomarker-guided patient selection, adaptive dosing to reduce toxicity, and refined pharmacodynamic monitoring to enhance therapeutic precision. Collectively, these insights support the rational integration of ATR–CHK1 inhibitors into clinical protocols for biomarker-defined gastric cancer subsets and underscore their promise Full article

Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating a growing cohort of younger survivors for whom post-treatment quality of life—notably reproductive function—is paramount. Curative treatments such as radical prostatectomy, pelvic radiotherapy, androgen-deprivation therapy (ADT), and chemotherapy often cause irreversible infertility via multiple mechanisms, including surgical disruption of the ejaculatory tract, endocrine suppression of spermatogenesis, direct gonadotoxic injury to the testes, and oxidative sperm DNA damage. Despite these risks, fertility preservation is frequently overlooked in pre-treatment counseling, leaving many patients unaware of their options. This narrative review synthesizes current evidence on how PCa therapies impact male fertility, elucidates the molecular and physiological mechanisms of iatrogenic infertility, and evaluates both established and emerging strategies for fertility preservation and restoration. Key interventions covered include sperm cryopreservation, microsurgical testicular sperm extraction (TESE), and assisted reproductive technologies (ART). Psychosocial factors influencing decision-making, novel biomarkers predictive of post-treatment spermatogenic recovery, and long-term offspring outcomes are also examined. The review underscores the urgent need for timely, multidisciplinary fertility consultation as a routine component of PCa care. As PCa increasingly affects men in their reproductive years, proactively integrating preservation into standard oncologic practice should become a standard survivorship priority. Full article

Oligometastatic non-small-cell lung cancer (OMD-NSCLC) has emerged as a biologically and clinically distinct subtype of advanced disease, characterized by limited metastatic burden and a more indolent course. In this narrative review, we examine the current definition of OMD-NSCLC, diagnostic tests, possible biomarkers, and current therapeutic strategies. Biological insights highlight the role of microRNAs in differentiating true oligometastatic state from polymetastatic disease. The main local ablative therapies (LAT) include surgery and radiotherapy. The integration of LAT with systemic therapies has been explored in clinical trials, yielding promising but occasionally inconsistent results. As the therapeutic landscape of OMD-NSCLC patients continues to evolve, refining definitions, identifying predictive biomarkers, and individualizing care are essential steps toward achieving the potential of radical-intent therapy. Full article

Background: Sex differences play a significant role in the epidemiology, biology, and outcomes of many cancers, including glioblastoma (GB), the most common and aggressive primary brain tumor. GB is more frequent in males, while females tend to have longer survival, though the underlying reasons for these differences remain poorly understood. Potential contributors include hormonal influences, sex-specific risk factors, and treatment disparities. Understanding these differences is critical for optimizing personalized treatment strategies. Methods: We conducted a retrospective analysis of patients with gliomas from a neuro-oncological database, with a primary focus on GB cases. Variables collected included sex, age, tumor type, molecular biomarker, and treatment modalities. The primary objective was to assess sex-based differences in tumor characteristics and outcomes, while the secondary objective was to identify predictors of time to progression and mortality. Results: The cohort comprised 125 GB, 48 astrocytomas, and 16 oligodendrogliomas, with no significant sex-based differences in age or tumor type distribution. Among GB patients, multifocality was more prevalent in females (14% vs. 8%; p = 0.01); also, EGFR amplification was more frequent in females (25.5% vs. 52.5%; p = 0.007). Males received chemotherapy (80% vs. 63%; p = 0.04) and radiotherapy (84% vs. 67%; p = 0.03) more frequently than females. Survival was positively associated with MGMT methylation (p = 0.002) and negatively associated with TERT mutation (p = 0.01). Multivariable analysis identified TERT mutation as a predictor of increased mortality (HR = 4.1; 95% CI: 1.2–14; p = 0.025), while multifocality predicted both mortality (HR = 2.3; 95% CI: 1.3–3.9; p = 0.003) and reduced time to progression (HR = 3.3; 95% CI: 1.02–10.6; p = 0.04). Conclusions: This study underscores the importance of sex and molecular profiling in GB management, revealing distinct patterns in tumor characteristics and treatment administration between males and females. Our findings advocate for the integration of sex-specific considerations and molecular profiling into clinical decision-making to improve outcomes for GB patients. Full article