Search Results (466)

Despite notable progress in cancer therapy, immune evasion remains a major obstacle to effective treatment outcomes. In the context of spaceflight, astronauts are exposed to unique environmental stressors—particularly microgravity and radiation—that profoundly affect cellular and immune homeostasis. Emerging evidence suggests that microgravity alters key cellular processes, including proliferation, apoptosis, adhesion, and oncogenic signaling pathways such as NF-κB and ERK1/2. Concurrently, microgravity (µg) disrupts immune regulation, potentially facilitating both tumor progression and treatment resistance. Of particular concern is the upregulation of human endogenous retroviruses (HERVs), especially HERV-K and HERV-W, under µg conditions, which may exacerbate inflammatory responses and immune system dysregulation. While some studies indicate that µg may impair tumor growth, others reveal enhanced immune evasion and reduced antitumor immunity. Importantly, insights from µg research extend beyond space medicine and provide translational opportunities for terrestrial oncology, including the development of physiologically relevant 3D tumor models for drug screening, the identification of mechano-sensitive pathways (FAK/RhoA, YAP/TAZ) as therapeutic targets, and novel immunotherapeutic strategies involving epigenetic modulation and checkpoint inhibition. This review critically examines the dual role of µg in modulating cancer progression and immune function. We synthesize findings on how µg shapes immune responses, alters tumor–immune system interactions, and impacts the efficacy of immunotherapeutic approaches. Finally, we highlight translational opportunities and challenges for optimizing cancer immunotherapy and precision oncology in both spaceflight and Earth-based environments. Full article

Primary cutaneous lymphomas (PCLs), including cutaneous T-cell lymphomas (CTCL) and primary cutaneous B-cell lymphomas (PCBCL), are a diverse group of non-Hodgkin lymphomas that primarily affect the skin. Radiotherapy (RT) plays a pivotal role in the treatment of these lymphomas, particularly for localized disease, due to its ability to deliver precise, skin-directed treatment. Mycosis fungoides (MF) and Sézary syndrome (SS), the most common subtypes of CTCL, often require skin-directed therapies such as electron beam therapy and superficial brachytherapy to manage localized lesions. Electron beam therapy, including total skin electron beam therapy (TSEBT), has been utilized for decades, offering high response rates but with the risk of cumulative skin toxicity. Recently, low-dose radiotherapy (LDRT) has gained attention as an effective alternative that reduces toxicity while maintaining durable responses. Superficial brachytherapy is another modality that delivers radiation through custom molds, allowing for homogeneous dosing over complex anatomical areas like the face. Both teleradiotherapy and brachytherapy have demonstrated high complete response rates, with low recurrence rates observed when higher doses are used. In the context of primary cutaneous B-cell lymphomas, such as primary cutaneous marginal zone lymphoma (PCMZL) and primary cutaneous follicle center lymphoma (PCFCL), radiotherapy also offers excellent local control, particularly for indolent subtypes. However, more aggressive subtypes, such as diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), may require systemic therapies in addition to radiation. Overall, teleradiotherapy and brachytherapy are essential components of the therapeutic arsenal for primary cutaneous lymphomas, offering effective disease control with manageable toxicity, while ongoing research focuses on optimizing treatment strategies and exploring novel combinations with systemic therapies. Full article

Background: Stereotactic body radiation therapy (SBRT) has proven effective in controlling spinal lesions with minimal toxicity, primarily due to its ability to limit spinal cord dose. Recent advances in MR-linac (MRL) technology offer superior spinal cord visualization and real-time gating, which can facilitate dose escalation in spinal tumor treatment while maintaining safety. Purpose: This study aimed to optimize motion management for spine SBRT on an MRL by analyzing patient-specific motion dynamics and evaluating the most effective registration structures. We hypothesized that baseline shifts (BLS) would improve delivery efficiency while maintaining spinal cord dose constraints. The goal was to establish displacement thresholds and assess the role of baseline shift correction adaptative planning in improving treatment delivery efficiency. Methods: Twelve patients underwent two MRI sessions on the MRL. The optimal registration structure was identified, and intrafraction motion was assessed to calculate delivery efficiency. Baseline shift (BLS) simulations were applied for five cases that showed significant motion and suboptimal delivery efficiency, and the dosimetric impact of the BLS was evaluated. The simulated BLS-based plan adaptation was implemented via a segment aperture morphing adapt-to-position workflow. Results: The most stable registration structure was the spinal canal plus three adjacent vertebrae. Cine imaging revealed average intrafraction motion (95th to 5th percentiles) of 0.8 ± 0.5 mm in the right-left (RL) direction, 0.9 ± 0.6 mm in the anterior–posterior (AP) direction, and 0.7 ± 0.5 mm in the SI direction. Simulated BLS improved delivery efficiency to >80% in all but one case, with a ±1 mm displacement threshold tolerance. While target coverage remained consistent after BLS simulation, the spinal cord dose increased by 7–60%, exceeding the 14 Gy constraint in three of the five simulated cases. Conclusions: Cine imaging and BLS can enhance delivery efficiency in spine SBRT but may increase spinal cord dose. These findings underscore the need for careful patient selection, advanced motion management, and patient-specific BLS protocols. Full article

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease (ILD) with poor prognosis and limited therapeutic options. The introduction of antifibrotic agents has improved survival outcomes in IPF patients, which has led to more frequent recognition of comorbidities, particularly lung cancer (LC). This review summarizes current evidence on the epidemiology and pathogenesis of LC in the context of IPF, with particular emphasis placed on shared molecular, cellular, genetic, and epigenetic alterations. Diagnostic approaches and available treatment modalities, including surgical, systemic, and radiation therapies, are outlined, and their limitations in patients with IPF-LC are discussed. Acute exacerbations (AEs), as a life-threatening complication influencing diagnostic and treatment strategies, are specifically addressed. Moreover, studies indicating a possible protective effect of antifibrotic agents against LC development in IPF are reviewed. Further research is warranted into the shared mechanisms of IPF and LC to identify novel therapeutic targets. Establishing standardized, multidisciplinary clinical guidelines is essential for optimizing patient management, reducing AE risk, and improving patient outcomes. Full article

This report presents the case of a seven-year-old West Highland White Terrier diagnosed with relapsed and refractory multiple myeloma (MM), managed using multiple treatment approaches, including conventional chemotherapy (melphalan, vincristine, doxorubicin, and dexamethasone), radiation therapy (RT), and novel agents such as the selective inhibitor of nuclear export (verdinexor), proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), and tyrosine kinase inhibitors (TKIs; toceranib and sorafenib). Treatment response was monitored using serum globulin concentration and imaging studies. Verdinexor achieved the longest period of stable remission with minimal toxicity post-RT. Bortezomib + dexamethasone was effective in controlling hyperglobulinemia at doses ≥ 1.45 mg/m², although cumulative hematologic and gastrointestinal toxicity limited its prolonged use. Second-line proteasome inhibitors and TKIs demonstrated limited efficacy. Despite initial therapeutic response, the patient’s condition deteriorated due to persistent hyperglobulinemia and hyperviscosity syndrome. The absence of advanced supportive options, including plasmapheresis, contributed to a fatal outcome. This case highlights the potential utility of novel therapies such as verdinexor and bortezomib in managing refractory canine MM. Timely intervention, individualized dosing, and supportive care are essential for optimizing treatment outcomes. Further research is required to define effective combinations and integrate advanced care options, including stem cell transplantation and targeted antibody therapies, in veterinary MM. Full article

Despite the increasing number of novel therapies to treat newly diagnosed multiple myeloma (NDMM), preventing skeletal-related events (SREs) remains a challenge. This review summarizes the mechanistic causes of myeloma bone disease, data supporting the use of bisphosphonates and RANKL inhibitors, and the optimal management of preventing SREs in NDMM patients. Both zoledronic acid (ZA) and denosumab are acceptable treatment options with comparable safety and efficacy profiles. However, in patients who are candidates for autologous stem cell transplant (ASCT), denosumab may be preferred over ZA due to a progression-free survival (PFS) benefit observed in post hoc analyses when used with proteasome inhibitor-based regimens. The optimal duration of bone-directed therapy is unclear, but it is typically given for two years. Supportive care should include dental evaluation at baseline, annually, and if symptoms appear, given the risk for jaw osteonecrosis with both ZA and denosumab. Both drugs should be held in the setting of dental work. Patients should receive adequate calcium and vitamin D supplementation. Supportive procedures such as cement augmentation, radiation, and orthopedic surgery can also help treat compression fractures, uncontrolled pain, cord compression, and pathologic fractures. We conclude with our approach for managing SREs and a review of novel therapies and targets. Full article

Microtubules play a key role in cell division and cell migration. Thus, microtubule-targeting agents (MTAs) are pivotal in cancer therapy due to their ability to disrupt cell division microtubule dynamics. Traditionally divided into stabilizers and destabilizers, MTAs are increasingly being repurposed for central nervous system (CNS) applications, including brain malignancies such as gliomas and neurodegenerative diseases like Alzheimer’s and Parkinson’s. Microtubule-stabilizing agents, such as taxanes and epothilones, promote microtubule assembly and have shown efficacy in both tumour suppression and neuronal repair, though their CNS use is hindered by blood–brain barrier (BBB) permeability and neurotoxicity. Destabilizing agents, including colchicine-site and vinca domain binders, offer potent anticancer effects but pose greater risks for neuronal toxicity. This review highlights the mapping of nine distinct tubulin binding pockets—including classical (taxane, vinca, colchicine) and emerging (tumabulin, pironetin) sites—that offer new pharmacological entry points. We summarize the recent advances in structural biology and drug design, enabling MTAs to move beyond anti-mitotic roles, unlocking applications in both cancer and neurodegeneration for next-generation MTAs with enhanced specificity and BBB penetration. We further discuss the therapeutic potential of combination strategies, including MTAs with radiation, histone deacetylase (HDAC) inhibitors, or antibody–drug conjugates, that show synergistic effects in glioblastoma models. Furthermore, innovative delivery systems like nanoparticles and liposomes are enhancing CNS drug delivery. Overall, MTAs continue to evolve as multifunctional tools with expanding applications across oncology and neurology, with future therapies focusing on optimizing efficacy, reducing toxicity, and overcoming therapeutic resistance in brain-related diseases. Full article

This study investigated the evolving trends, current research hotspots, and future directions of radiotherapy combined with nanobiomaterials through a bibliometric analysis. Publications related to nanobiomaterials used in radiotherapy between 2004 and 2024 were retrieved from the Web of Science Core Collection database and analyzed using VOSviewer, R, and CiteSpace. China emerged as the leading contributor, accounting for 1051 publications (50.41%), followed by the USA. Liu Zhuang is the most productive author in this field. American Chemical Society (ACS) Nano published the most influential articles and accumulated the highest number of citations. Advanced Targeted Therapies in Cancer: Drug Nanocarriers, the Future of Chemotherapy was the most cited, with 1255 citations. Citation bursts have revealed emerging research trends in targeted delivery, cellular studies, co-delivery strategies, immunogenic cell death, polymeric nanoparticles, tumor research, and drug delivery systems, indicating potential avenues for future research. Over the past two decades, nanomaterials for radiotherapy have gained substantial attention. Key areas of focus include enhancing the efficacy of radiotherapy, achieving targeted drug delivery, minimizing adverse effects, and integrating nanomaterials with other therapeutic modalities. Future investigations are expected to improve the precision of radiotherapy, augment radiation effects, and optimize the tumor microenvironment. Full article

Introduction: Actinic cheilitis (AC) is a common precancerous condition affecting the lips, primarily caused by prolonged ultraviolet radiation exposure. Various treatment options are available. However, the optimal treatment approach remains a subject of debate. Objective: To summarize and compare practice-relevant interventions for AC. Materials and Methods: A pre-defined protocol was registered in PROSPERO (CRD42021225182). Systematic searches in Medline, Embase, and Central, along with manual trial register searches, identified studies reporting participant clearance rates (PCR) or recurrence rates (PRR). Quality assessment for randomized controlled trials (RCTs) was conducted using the Cochrane Risk of Bias tool 2. Uncontrolled studies were evaluated using the tool developed by the National Heart, Lung, and Blood Institute. The generalized linear mixed model was used to pool proportions for uncontrolled studies. A pairwise meta-analysis for RCTs was applied, using the odds ratio (OR) as the effect estimate and the GRADE approach to evaluate the quality of the evidence. Adverse events were analyzed qualitatively. Results: A comprehensive inclusion of 36 studies facilitated an evaluation of 614 participants for PCR, and 430 patients for PRR. Diclofenac showed the lowest PCR (0.53, 95% confidence interval (CI) [0.41; 0.66]), while CO₂ laser showed the highest PCR (0.97, 95% CI [0.90; 0.99]). For PRR, Er:YAG laser showed the highest rates (0.14, 95% CI [0.08; 0.21]), and imiquimod the lowest (0.00, 95% CI [0.00; 0.06]). In a pairwise meta-analysis, the OR indicated a lower recurrence rate for Er:YAG ablative fractional laser (AFL)-primed methyl-aminolevulinate photodynamic therapy (MAL-PDT) (Er:YAG AFL-PDT) compared to methyl-aminolevulinate photodynamic therapy (MAL-PDT) alone (OR = 0.22, 95% CI [0.06; 0.82]). The CO₂ laser showed fewer local side effects than the Er:YAG laser, while PDTs caused more skin reactions. Due to qualitative data, comparability was limited, highlighting the need for individualized treatment. Conclusions: This study provides a complete and up-to-date evidence synthesis of practice-relevant interventions for AC, identifying the CO₂ laser as the most effective treatment and regarding PCR and imiquimod as most effective concerning PRR. Full article

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, necessitating novel therapeutic approaches. Oncolytic treatments, particularly oncolytic viruses (OVs), have emerged as promising candidates by selectively infecting and lysing tumor cells while stimulating anti-tumor immunity. Various virus-based therapies are under investigation, including genetically engineered herpes simplex virus (HSV), adenovirus, poliovirus, reovirus, vaccinia virus, measles virus, and Newcastle disease virus, each exploiting unique tumor-selective mechanisms. While some, such as HSV-based therapies including G207 and Delytact^TM, have demonstrated clinical progress, significant challenges persist, including immune evasion, heterogeneity in patient response, and delivery barriers due to the blood–brain barrier. Moreover, combination strategies integrating OVs with immune checkpoint inhibitors, chemotherapy, and radiation are promising but require further clinical validation. Non-viral oncolytic approaches, such as tumor-targeting bacteria and synthetic peptides, remain underexplored. This review highlights current advancements while addressing critical gaps in the literature, including the need for optimized delivery methods, better biomarker-based patient stratification, and a deeper understanding of GBM’s immunosuppressive microenvironment. Future research should focus on enhancing OV specificity, engineering viruses to deliver therapeutic genes, and integrating OVs with precision medicine strategies. By identifying these gaps, this review provides a framework for advancing oncolytic therapies in GBM treatment. Full article

Purpose: To present the findings of our preliminary experience using daily image-guided radiotherapy (IGRT) supported by implanted fiducial markers (FMs) in the radiotherapy of the vaginal cuff, in a cohort of post-surgery endometrial cancer patients. Methods: Patients with vaginal cuff cancer requiring adjuvant radiation with external beams were enrolled. Five patients underwent radiation therapy targeting the pelvic disease and positive lymph nodes, with doses of 50.4 Gy in twenty-eight fractions and a subsequent stereotactic boost on the vaginal vault at a dose of 5 Gy in a single fraction. One patient was administered 30 Gy in five fractions to the vaginal vault. These patients underwent external beam RT following the implantation of three 0.40 × 10 mm gold fiducial markers (FMs). Our IGRT strategy involved real-time 2D kV image-based monitoring of the fiducial markers during the treatment delivery as a surrogate of the vaginal cuff. To explore the potential role of FMs throughout the treatment process, we analyzed cine movies of the 2D kV-triggered images during delivery, as well as the image registration between pre- and post-treatment CBCT scans and the planning CT (pCT). Each CBCT used to trigger fraction delivery was segmented to define the rectum, bladder, and vaginal cuff. We calculated a standard metric to assess the similarity among the images (Dice index). Results: All the patients completed radiotherapy and experienced good tolerance without any reported acute or long-term toxicity. We did not observe any loss of FMs during or before treatment. A total of twenty CBCTs were analyzed across ten fractions. The observed trend showed a relatively emptier bladder compared to the simulation phase, with the bladder filling during the delivery. This resulted in a final median Dice similarity coefficient (DSC) of 0.90, indicating strong performance. The rectum reproducibility revealed greater variability, negatively affecting the quality of the delivery. Only in two patients, FMs showed intrafractional shift > 5 mm, probably associated with considerable rectal volume changes. Target coverage was preserved due to a safe CTV-to-PTV margin (10 mm). Conclusions: In our preliminary study, CBCT in combination with the use of fiducial markers to guide the delivery proved to be a feasible method for IGRT both before and during the treatment of post-operative gynecological cancer. In particular, this approach seems to be promising in selected patients to facilitate the use of SBRT instead of BRT (brachytherapy), thanks to margin reduction and adaptive strategies to optimize dose delivery while minimizing toxicity. A larger sample of patients is needed to confirm our results. Full article

Background: Lung cancer ranks as the leading cause of cancer-related mortality worldwide. The complexity of tumor delineation, crucial for radiation therapy, requires expertise often unavailable in resource-limited settings. Artificial Intelligence (AI), particularly with advancements in deep learning (DL) and natural language processing (NLP), offers potential solutions yet is challenged by high false positive rates. Purpose: The Oncology Contouring Copilot (OCC) system is developed to leverage oncologist expertise for precise tumor contouring using textual descriptions, aiming to increase the efficiency of oncological workflows by combining the strengths of AI with human oversight. Methods: Our OCC system initially identifies nodule candidates from CT scans. Employing Language Vision Models (LVMs) like GPT-4V, OCC then effectively reduces false positives with clinical descriptive texts, merging textual and visual data to automate tumor delineation, designed to elevate the quality of oncology care by incorporating knowledge from experienced domain experts. Results: The deployment of the OCC system resulted in a 35.0% reduction in the false discovery rate, a 72.4% decrease in false positives per scan, and an F1-score of 0.652 across our dataset for unbiased evaluation. Conclusions: OCC represents a significant advance in oncology care, particularly through the use of the latest LVMs, improving contouring results by (1) streamlining oncology treatment workflows by optimizing tumor delineation and reducing manual processes; (2) offering a scalable and intuitive framework to reduce false positives in radiotherapy planning using LVMs; (3) introducing novel medical language vision prompt techniques to minimize LVM hallucinations with ablation study; and (4) conducting a comparative analysis of LVMs, highlighting their potential in addressing medical language vision challenges. Full article

Despite advances in surgery, chemotherapy, and radiation treatments for pancreatic ductal adenocarcinoma (PDAC), 5-year survival rates remain at nearly 11%. Cholangiocarcinoma, while not as severe, also possesses similar survival rates. Fewer than 20% of patients are surgical candidates at time of diagnosis; therefore, it is imperative that alternative therapies are effective for non-surgical patients. There are several thermal ablative techniques, including radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFU), microwave ablation (MWA), alcohol ablation, stereotactic body radiotherapy (SBRT), cryoablation, irreversible electroporation (IRE), biliary intraluminal brachytherapy, and biliary photodynamic therapy (PDT). Emerging literature in animal models and human patients has demonstrated that endoscopic ultrasound (EUS)-guided RFA (EUS-RFA) prevents tumor progression through coagulative necrosis, protein denaturation, and activation of anticancer immunity in local and distant tumor tissue (abscopal effect). RFA treatment has been shown to not only reduce tumor-associated immunosuppressive cells but also increase functional T cells in distant tumor cells not treated with RFA. The remarkable ability to reduce tumor progression and promote tumor microenvironment (TME) remodeling makes RFA a very promising non-surgical therapy technique that has the potential to reduce mortality in this patient population. EUS-RFA offers superior precision and safety compared to other ablation techniques for pancreatic and biliary cancers, due to real-time imaging capabilities and minimally invasive nature. Future research should focus on optimizing RFA protocols, exploring combination therapies with chemotherapy or immunotherapy, and expanding its use in patients with metastatic disease. This review article will explore the current data and underlying pathophysiology of EUS-RFA while also highlighting the role of ablative therapies as a whole in immune activation response. Full article

Targeted radionuclide therapy (TRT) utilizes radiopharmaceuticals to deliver radiation directly to cancer cells while sparing healthy tissues. Beyond the absorbed dose of ablative radiation, TRT induces non-targeted effects (NTEs) that significantly enhance its therapeutic efficacy. These effects include radiation-induced bystander effects (RIBEs), abscopal effects (AEs), radiation-induced genomic instability (RIGI), and adaptive responses, which collectively influence the behavior of cancer cells and the tumor microenvironment (TME). TRT also modulates immune responses, promoting immune-mediated cell death and enhancing the efficacy of combination therapies, such as the use of immune checkpoint inhibitors. The molecular mechanisms underlying TRT involve DNA damage, oxidative stress, and apoptosis, with repair pathways like homologous recombination (HR) and non-homologous end joining (NHEJ) playing critical roles. However, challenges such as tumor heterogeneity, hypoxia, and radioresistance limit the effectiveness of this approach. Advances in theranostics, which integrate diagnostic imaging with TRT, have enabled personalized treatment approaches, while artificial intelligence and improved dosimetry offer potential for treatment optimization. Despite the significant survival benefits of TRT in prostate cancer and neuroendocrine tumors, 30–40% of patients remain unresponsive, which highlights the need for further research into molecular pathways, long-term effects, and combined therapies. This review outlines the dual mechanisms of TRT, direct toxicity and NTEs, and discusses strategies to enhance its efficacy and expand its use in oncology. Full article

Background/Objectives: Proton therapy delivers highly conformal doses to the target area without producing an exit dose, minimizing cumulative doses to healthy liver tissue. This study aims to evaluate current practices, challenges, and variations in the implementation of proton stereotactic body radiation therapy (SBRT) and hypofractionated therapy for liver malignancies, with the goal of providing a technical assessment to promote broader adoption and support future clinical trials. Methods and Materials: An extensive survey was conducted by NRG Oncology across North American proton treatment centers to assess the current practices of proton liver SBRT and hypofractionated therapy. The survey focused on key aspects, including patient selection, prescription and normal tissue constraints, simulation and motion management, treatment planning, quality assurance (QA), treatment delivery, and the use of image-guided radiation therapy (IGRT). Results: This survey captures the current practice patterns and status of proton SBRT and hypofractionated therapy in liver cancer treatment.  Proton therapy is increasingly preferred for treating inoperable liver malignancies due to its ability to minimize healthy tissue exposure. However, the precision required for proton therapy presents challenges, particularly in managing uncertainties and target motion during high-dose fractions and short treatment courses. Survey findings revealed significant variability in clinical practices across centers, highlighting differences in motion management, dose fractionation schedules, and QA protocols. Conclusion: Proton SBRT and hypofractionated therapy offer significant potential for treating liver malignancies. A comprehensive approach involving precise patient selection, treatment planning, and QA is essential for ensuring safety and effectiveness. This survey provides valuable insights into current practices and challenges, offering a foundation for technical recommendations to optimize the use of proton therapy and guide future clinical trials. Full article