Search Results (141)

Background: Radiation dose escalation for locally advanced pancreatic cancer (LAPC) using stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) or computed tomography (CT)-guided moderately hypofractionated ablative radiation therapy (HART) can achieve favorable outcomes although have not previously been compared. Methods: We performed a multi-center retrospective analysis of SMART (50 Gy/5 fractions) vs. HART (75 Gy/25 fractions or 67.5 Gy/15 fractions with concurrent capecitabine) for LAPC. Gray’s test and Cox proportional regression analyses were performed to identify factors associated with local failure (LF) and overall survival (OS). Results: A total of 211 patients (SMART, n = 91; HART, n = 120) were evaluated, and none had surgery. Median follow-up after SMART and HART was 27.0 and 40.0 months, respectively (p < 0.0002). SMART achieved higher gross tumor volume (GTV) coverage and greater hotspots. Two-year LF after SMART and HART was 6.5% and 32.9% (p < 0.001), while two-year OS was 31.0% vs. 35.3% (p = 0.056), respectively. LF was associated with SMART vs. HART (HR 5.389, 95% CI: 1.298–21.975; p = 0.021) and induction mFOLFIRINOX vs. non-mFOLFIRINOX (HR 2.067, 95% CI 1.038–4.052; p = 0.047), while OS was associated with CA19-9 decrease > 40% (HR 0.725, 95% CI 0.515–0.996; p = 0.046) and GTV V120% (HR 1.022, 95% CI 1.006–1.037; p = 0.015). Acute grade > 3 toxicity was similar (3.3% vs. 5.8%; p = 0.390), while late grade > 3 toxicity was less common after SMART (2.2% vs. 9.2%; p = 0.037). Conclusions: Ablative SMART and HART both achieve favorable oncologic outcomes for LAPC with minimal toxicity. We did not observe an OS difference, although technical advantages of SMART might improve target coverage and reduce LF. Full article

Pulmonary hypertension (PH) is broadly defined as a mean pulmonary arterial pressure (mPAP) exceeding 20 mm Hg at rest. Pulmonary arterial hypertension (PAH) is a specific subset of PH characterized by a normal pulmonary arterial wedge pressure (PAWP), combined with elevated mPAP and increased pulmonary vascular resistance (PVR), without other causes of pre-capillary hypertension such as lung diseases or chronic thromboembolic pulmonary hypertension. The majority of PAH cases are idiopathic; other common etiologies include connective tissue disease-associated PAH, congenital heart disease, and portopulmonary hypertension. To a lesser extent, genetic and familial forms of PAH can also occur. The pathophysiology of PAH involves the following four primary pathways: nitric oxide, endothelin-1, prostacyclin, and activin/bone morphogenetic protein (BMP). Dysregulation of these pathways leads to a progressive vasculopathy marked by vasoconstriction, vascular proliferation, elevated right heart afterload, and ultimately right-sided heart failure. Diagnosing PAH is challenging and often occurs at advanced stages. The gold standard for diagnosis remains invasive right heart catheterization. Along with invasive hemodynamic measurements, several noninvasive imaging modalities such as echocardiography and ventilation-perfusion scanning are key adjunct techniques. Also, recent advancements in cardiac magnetic resonance (CMR) have opened a new era for PAH management. Additionally, CMR and echocardiography not only enable diagnosis but also aid in evaluating disease severity and monitoring treatment responses. Current PAH treatments focus on targeting molecular pathways, reducing inflammation, and inhibiting right-sided heart failure. Integrating imaging with basic science techniques is crucial for enhanced patient diagnosis, and precision medicine is emerging as a key strategy in PAH management. Additionally, the incorporation of artificial intelligence into both molecular and imaging approaches holds significant potential. There is a growing need to integrate new imaging modalities with high resolution and reduced radiation exposure into clinical practice. In this review, we discuss the molecular pathways involved in PAH, the imaging modalities utilized for diagnosis and monitoring, and current targeted therapies. Advances in molecular understanding and imaging technologies, coupled with precision medicine, could hold promise in improving patient outcomes and revolutionizing the management of PAH patients. Full article

Background: Immediate direct-to-implant (DTI) breast reconstruction is associated with high patient satisfaction and faster recovery. However, concerns remain for patients requiring post-mastectomy radiation therapy (PMRT). While PMRT improves overall survival for breast cancer patients, it has been associated with increased implant-specific complications such as capsular contracture, infection, and implant loss. As the impact of PMRT on pre-pectoral DTI specifically is not well understood, the goal of this systematic review was to evaluate the impact of PMRT on outcomes in this growing patient population. Methods: PubMed, EMBASE, and Web of Science were systematically reviewed for articles published from 1 January 2000 to 23 December 2024 investigating outcomes after prepectoral DTI reconstruction with exposure to PMRT. Demographic, clinical, and post-operative variables were recorded for PMRT and non-PMRT cohorts, and primary outcomes included infection, capsular contracture, implant loss, and wound healing complications. Meta-analysis was performed for key outcomes using the Mantel-Haenszel method. Results: Of 472 initially identified records, seven studies met inclusion criteria with a combined total of 343 prepectoral DTI reconstructions exposed to PMRT and 1385 reconstructions not exposed to PMRT. PMRT significantly increased the odds of any complication (OR 2.11, p = 0.01), implant loss (OR 1.88, p = 0.02), infection (OR 2.76, p = 0.004), and capsular contracture (OR 8.88, p < 0.001). However, PMRT was not associated with significantly increased odds of wound healing complications (OR 1.5, p = 0.36). Conclusions: PMRT after pre-pectoral DTI reconstruction significantly increases odds of complications, including infection, capsular contracture, and reconstructive failure. Plastic surgeons should be mindful of the sequelae of PMRT with prepectoral DTI reconstruction to improve pre-operative counseling and shared decision-making. Full article

One of the most common malignant tumors worldwide is lung cancer, and it is associated with the highest death rate among all cancers. Traditional treatment options for lung cancer include radiation, chemotherapy, targeted therapy, and surgical resection. However, the survival rate is low, and the outlook is still dreadfully dire. The pursuit of a paradigm change in treatment approaches is, therefore, imperative. Tyrosine kinases (TKs), a subclass of protein kinases, regulate vital cellular function by phosphorylating tyrosine residues in proteins. Mutations, overexpression, and autocrine paracrine stimulation can transform TKs into oncogenic drivers, causing cancer pathogenesis. Tyrosine kinase inhibitors (TKIs) have emerged as an attractive targeted therapy option, especially for non-small cell lung cancer (NSCLC). However, resistance to TKIs, and adverse cardiovascular effects such as heart failure, atrial fibrillation, hypertension, and sudden death, are among the most common adverse effects of TKIs. There is increasing interest in plant-derived natural products in the hunt for powerful chemosensitizer and pathway modulators for enhancing TKI activity and/or overcoming resistance mechanisms. This highlights the mechanism of TKs’ activation in cancer, the role of TKIs in NSCLC mechanisms, and the challenges posed by TKI-acquired resistance. Additionally, we explored various plant-derived natural products’ bioactive compounds with the chemosensitizer and pathway-modulating potential with TKs’ inhibitory and anticancer effects. Our review suggests that a combination of natural products with TKIs may provide a novel and promising strategy for overcoming resistance in lung cancer. In future, further preclinical and clinical studies are advised. Full article

Locally advanced rectal cancer treatment has shifted toward personalized, risk-adapted strategies that balance oncologic control with functional preservation while minimizing toxicity. A multidisciplinary team approach is essential, tailoring treatment guided by individual patient risk factors and priorities. Traditional neoadjuvant chemoradiation and subsequent total mesorectal excision has improved local control, but concerns remain regarding systemic failure and treatment-related morbidity. Total neoadjuvant therapy is now widely considered a preferred approach for more advanced tumors, enhancing systemic control, improving chemotherapy compliance, and facilitating organ preservation in select patients. Recent studies highlight that response-based treatment adaptation allows for better patient stratification, with selected patients who respond well to preoperative chemotherapy potentially omitting radiation without compromising outcomes and omitting surgery for patients with complete clinical responses to chemoradiation and chemotherapy. Advances in molecular profiling, particularly in mismatch repair deficiency or microsatellite instability-high tumors, have enabled the implementation of immune checkpoint inhibitors, permitting select patients to avoid both radiation and surgery, thereby reducing treatment-related toxicities. Future research should focus on validating predictive biomarkers, such as circulating tumor DNA, refining patient selection, and optimizing treatment monitoring while also developing novel therapeutic strategies to further personalize locally advanced rectal cancer management. Full article

Given the promising outcomes of stereotactic body radiation therapy (SBRT) in treating colorectal cancer liver metastases (CRLMs), we proposed an innovative strategy combining surgery with planned liver SBRT for CRLMs. This retrospective study included patients who underwent curative-intent surgery combined with planned liver SBRT from July 2019 to October 2023. Planned liver SBRT was delivered to residual unresectable and unablatable lesions with maximum diameters of ≤5 cm. Outcomes included local failure (LF), intrahepatic recurrence-free survival (IHRFS), extrahepatic recurrence-free survival (EHRFS), progression-free survival (PFS), overall survival (OS), and radiation-related adverse events. A total of 69 patients were included. The 1-, and 2-year cumulative incidence rates of LF after SBRT were 7.7%, and 9.6%, respectively. The median PFS was 6.2 months, and the median OS was 45.8 months. Multivariate analysis identified RAS/BRAF mutations, extrahepatic metastases excluding lung involvement, and higher CEA as independent predictors of poorer OS. Intrahepatic recurrence was the predominant pattern of first disease progression after combination treatment. Acute grade 1–2 radiation-related adverse events occurred in 56.5% of patients, while grade 3 toxicities were reported in 4.3%. This approach offers favorable long-term outcomes, suggesting its potential to broaden the indications for curative-intent local treatments in CRLMs. Full article

Background: High-dose γ-ray exposure (≥7 Gy) in nuclear emergencies induces life-threatening acute radiation syndrome, characterized by rapid hematopoietic collapse (leukocytes <0.5 × 10⁹/L) and gastrointestinal barrier failure. While clinical biomarkers like leukocyte depletion guide current therapies targeting myelosuppression, the concomitant metabolic disturbances and gut microbiota dysbiosis—critical determinants of delayed mortality—remain insufficiently profiled across the 28-day injury-recovery continuum. Methods: This study investigates the effects of ⁶⁰Co γ-ray irradiation on metabolic characteristics and gut microbiota in Sprague Dawley rats using untargeted metabolomics and 16S rRNA sequencing. Meanwhile, body weight and complete blood counts were measured. Results: Body weight exhibited significant fluctuations, with the most pronounced deviation observed at 14 days. Blood counts revealed a rapid decline in white blood cells, red blood cells, and platelets post-irradiation, reaching nadirs at 7–14 days, followed by gradual recovery to near-normal levels by 28 days. Untargeted metabolomics identified 32 upregulated and 33 downregulated plasma metabolites at 14 days post-irradiation, while fecal metabolites showed 47 upregulated and 18 downregulated species at 3 days. Key metabolic pathways impacted included Glycerophospholipid metabolism, alpha-linolenic acid metabolism, and biosynthesis of unsaturated fatty acids. Gut microbiota analysis demonstrated no significant change in α-diversity but significant β-diversity shifts (p < 0.05), indicating a marked alteration in the compositional structure of the intestinal microbial community following radiation exposure. Principal coordinate analysis confirmed distinct clustering between control and irradiated groups, with increased abundance of Bacteroidota and decreased Firmicutes in irradiated rats. These findings highlight dynamic metabolic and microbial disruptions post-irradiation, with recovery patterns suggesting a 28-day restoration cycle. Spearman’s rank correlation analysis explored associations between the top 20 fecal metabolites and 50 abundant bacterial taxa. Norank_f_Muribaculaceae, Prevotellaceae_UCG-001, and Bacteroides showed significant correlations with various radiation-altered metabolites, highlighting metabolite–microbiota relationships post-radiation. Conclusions: This study provides insights into potential biomarkers for radiation-induced physiological damage and underscores the interplay between systemic metabolism and gut microbiota in radiation response. Full article

Background/Objectives: Glioblastoma (GBM) is an aggressive and lethal primary brain tumor with a poor prognosis, with a 5-year survival rate of approximately 5%. Despite advances in oncologic treatments, including surgery, radiotherapy, and chemotherapy, survival outcomes have remained stagnant, largely due to the failure of conventional therapies to address the tumor’s inherent heterogeneity. Radiomics, a rapidly emerging field, provides an opportunity to extract features from MRI scans, offering new insights into tumor biology and treatment response. This study evaluates the potential of delta radiomics, the study of changes in radiomic features over time in response to treatment or disease progression, exploring the potential of delta radiomics to track temporal radiation changes in tumor morphology and microstructure. Methods: A cohort of 50 female CD1 nude mice was injected intracranially with G7 glioblastoma cells and divided into irradiated (IR) and non-irradiated (non-IR) groups. MRI scans were performed at baseline (week 11) and post-radiation (weeks 12 and 14), and radiomic features, including shape, histogram, and texture parameters, were extracted and analyzed to capture radiation-induced changes. The most robust features were those identified through intra-observer reproducibility assessment, ensuring reliability in feature selection. A machine learning model was developed to classify irradiated tumors based on delta radiomic features, and statistical analyses were conducted to evaluate feature feasibility, stability, and predictive performance. Results: Our findings demonstrate that delta radiomics effectively captured significant temporal variations in tumor characteristics. Delta radiomics features exhibited distinct patterns across different time points in the IR group, enabling machine learning models to achieve a high accuracy. Conclusions: Delta radiomics offers a robust, non-invasive method for monitoring the treatment of glioblastoma (GBM) following radiation therapy. Future research should prioritize the application of MRI delta radiomics to effectively capture short-term changes resulting from intratumoral radiation effects. This advancement has the potential to significantly enhance treatment monitoring and facilitate the development of personalized therapeutic strategies. Full article

Risk priority number (RPN) is the most commonly used failure risk ranking method among all risk assessment methods. However, the traditional RPN method not only cannot handle incomplete information and hesitation information (such as hesitation information between the $s_5=\mathrm{L}\mathrm{o}\mathrm{w}$ and $s_6=\mathrm{M}\mathrm{o}\mathrm{d}\mathrm{e}\mathrm{r}\mathrm{a}\mathrm{t}\mathrm{e}$) provided by experts, but it also does not consider the objective weights of risk assessment factors. These reasons will lead to biased conclusions, causing decision makers to make wrong judgments. To address the limitations of the traditional RPN technique, the aim of this paper is to propose the flexible RPN assessment method under an uncertain environment. The flexible RPN assessment method is an extension of the traditional RPN technique. The flexible RPN method integrates the traditional RPN method and interval-valued 2-tuple weighted average method, and, simultaneously, considers subjective weights and objective weights. In the numerical verification, this study has adopted the example of stages of treatment planning for proton beam radiation therapy to verify the correctness and validity of the proposed flexible RPN technique. The numerical results show that the proposed flexible RPN technique not only handles the hesitation and incomplete information provided by experts but also considers the subjective and objective weights of risk assessment factors, providing more reasonable ranking results in the risk analysis. Full article

Squamous cell carcinoma is the most common malignancy affecting the sinonasal tract. Local recurrence is the main pattern of treatment failure, affecting nearly half of patients treated for primary sinonasal squamous cell carcinoma (SNSCC). Due to disease rarity and heterogeneity of practices, there are limited guidelines for how to diagnose and care for these patients. This paper reviews current evidence regarding etiology, pathophysiology, diagnosis, prognostic factors, and treatment modalities of recurrent SNSCC (rSNSCC). Currently, salvage surgery offers the only durable approach for eligible patients. These resections often require robust reconstructive options due to prior surgery or radiation. Chemoradiation is offered as an adjuvant or palliative approach when surgery is not a feasible option. Emerging options such as immunotherapy and particle therapy remain an area of ongoing investigation. Full article

Neonatal respiratory distress syndrome (RDS) is a common and potentially life-threatening condition in preterm infants, primarily due to surfactant deficiency. Early and accurate diagnosis is critical to guide timely interventions such as surfactant administration and respiratory support. Traditionally, chest X-rays have been used for diagnosis, but lung ultrasound (LUS) has gained prominence due to its non-invasive, radiation-free, and bedside applicability. Compared to chest X-rays and CT scans, LUS demonstrates superior sensitivity and specificity in diagnosing RDS, particularly in identifying surfactant need and predicting CPAP failure. Additionally, LUS offers real-time imaging without radiation exposure, an advantage over other modalities. However, its broader adoption is limited by challenges in standardizing training, ensuring diagnostic reproducibility, and validating scoring systems, especially in resource-limited settings. This narrative review aims to evaluate the role of LUS in the diagnosis and management of neonatal RDS over the past decade, focusing on its clinical utility, scoring systems, and emerging applications. We reviewed the literature from 2013 to 2023, focusing on studies evaluating LUS’ diagnostic accuracy, scoring systems, and its potential role in guiding surfactant therapy and predicting CPAP failure. Despite its benefits, addressing the variability in operator expertise and integrating artificial intelligence to enhance usability are crucial for ensuring LUS’ efficacy across diverse clinical environments. Future research should prioritize standardizing training and scoring protocols to facilitate wider implementation and optimize neonatal respiratory care outcomes. Full article

Infertility due to ovarian toxicity is a common side effect of cancer treatment in premenopausal women. Tamoxifen (TAM) is a selective estrogen receptor modulator that prevented radiation- and chemotherapy-induced ovarian failure in preclinical studies. In the current study, we examined the potential regulatory role of long noncoding RNAs (lncRNAs) in the mechanism of action of TAM in the ovaries of tumor-bearing rats receiving cyclophosphamide (CPA) as cancer therapy. We identified 166 lncRNAs, among which 49 were demonstrated to be differentially expressed (DELs) in the ovaries of rats receiving TAM and CPA compared to those receiving only CPA. A total of 24 DELs were upregulated and 25 downregulated by tamoxifen. The identified DELs shared the characteristics of noncoding RNAs described in other reproductive tissues. Eleven of the identified DELs displayed divergent modes of action, regulating target transcripts via both cis- and trans-acting pathways. Functional enrichment analysis revealed that, among target genes ascribed to the identified DELs, the majority were involved in apoptosis, cell adhesion, immune response, and ovarian aging. The presented data suggest that the molecular mechanisms behind tamoxifen’s protective effects in the ovaries may involve lncRNA-dependent regulation of critical signaling pathways related to inhibition of follicular transition and ovarian aging, along with the suppression of apoptosis and regulation of cell adhesion. Employing a tumor-bearing animal model undergoing chemotherapy, which accurately reflects the conditions of mammary cancer, reinforces the obtained results. Given that tamoxifen remains a key player in the management and prevention of breast cancer, understanding its ovarian-specific actions in cancer patients is crucial and requires detailed functional studies to clarify the underlying molecular mechanisms. Full article

We present the case of a 60-year-old male with recurrent atypical meningioma in the right parietal lobe, previously treated with surgery and radiation therapy. Magnetic resonance imaging (MRI) performed 5 years after radiation therapy suggested a possible recurrence. A somatostatin receptor positron emission tomography/computed tomography (SR-PET/CT) scan with Gallium-68 DOTATATE was performed to confirm this suspicion. SR-PET/CT confirmed the presence of recurrent meningioma, showing a novel “rosary sign” with multiple adjacent areas of focal tracer uptake along the resection margins of the previous surgical site in the right parietal region. This novel imaging pattern improved diagnostic accuracy by detailing disease extent and identifying additional lesions not visible via MRI. Given the failure of prior treatments and high SR expression, peptide receptor radionuclide therapy (PRRT) was proposed as a therapeutic option for the patient. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Surgical resection is the most reliable chance for cure, but high rates of positive margins and local failure persist. Neoadjuvant therapies (NAT), including chemotherapy and radiation therapy (RT), are being explored to improve surgical outcomes, particularly in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). This review aims to summarize the current landscape and future directions for neoadjuvant RT (NART) in PDAC. Methods: The review includes a detailed analysis of past and ongoing clinical trials investigating various NART approaches in PDAC, with an emphasis on different RT techniques, fractionation schemes, and their integration into multimodal treatment strategies. Results: Early evidence suggests that NART can improve resection margins and local control. However, recent trials, including the Alliance A021501 and LAP-07 trials, have failed to demonstrate significant survival benefits with the addition of RT to NAT. Nevertheless, nuances in trial design and execution continue to keep the question of NART open. Newer approaches, such as stereotactic magnetic resonance-guided adaptive radiation therapy (SMART), show promise in improving local control and survival, but further phase 3 trials are needed. Conclusions: While NART has shown potential in improving local control in PDAC, its impact on overall survival remains unclear. Ongoing trials, particularly those utilizing advanced techniques like SMART, are critical in defining the role of RT in the neoadjuvant setting for PDAC. Collaboration across multidisciplinary teams is essential to optimize treatment strategies and trial outcomes. Full article

Background: Radiation therapy is a crucial component of breast cancer treatment. However, it is well known to increase the risk of unsatisfactory cosmetic outcomes and higher complication rates. The aim of this study is to provide further insight into the use of acellular dermal matrices (ADMs) for the prevention of capsular contracture. Materials and Methods: This single-center, retrospective study analyzed irradiated patients who underwent post-mastectomy, ADM-assisted implant reconstructions. Of the 60 patients included, 26 underwent expander-to-implant substitution after radiotherapy (Group A), while 34 required implant replacement due to capsular contracture following radiotherapy (Group B). The primary objective was to evaluate the effectiveness of ADMs in reducing reconstructive failures, complications, and capsular contracture after breast irradiation. Results: We recorded a total of 15 complications and four implant losses. Reconstructive failures were attributed to implant exposure in two cases, full-thickness skin necrosis in one case, and severe Baker grade IV contracture in one case. Both Group A and Group B showed a significant decrease in postoperative Baker grades. US follow-up was used to demonstrate ADM integration with host tissues over time. Conclusions: Based on our findings, the use of ADM in selected cases appears to be a viable option for treating and preventing capsular contracture in irradiated breasts. This approach is associated with relatively low complication rates, a low rate of reconstructive failure, and satisfactory cosmetic outcomes and can be applied both in breast reconstructed with implants and with expanders. Full article