Search

Introduction: One of the most feared side effects of radiotherapy (RT) in the setting of breast cancer (BC) patients is cardiac toxicity. This side effect can jeopardize the quality of life (QoL) of long-term survivors. The impact of modern techniques of RT such as deep inspiration breath hold (DIBH) have dramatically changed this setting. We report and discuss the results of the literature overview of this paper. Materials and methods: Literature references were obtained with a PubMed query, hand searching, and clinicaltrials.gov. Results: We reported and discussed the toxicity of RT and the improvements due to the modern techniques in the setting of BC patients. Conclusions: BC patients often have a long life expectancy, thus the RT should aim at limiting toxicities and at the same time maintaining the same high cure rates. Further studies are needed to evaluate the risk–benefit ratio to identify patients at higher risk and to tailor the treatment choices. [ABSTRACT FROM AUTHOR]

External beam radiation therapy with conventional fractionation to a total dose of 76-80 Gy represents th emost adopted treatment modality for prostate cancer. Dose escalation in this setting has been demonstrated to improve biochemical control with acceptable toxicity using contemporary radiotherapy techniques. Hypofractionated radiotherapy and stereotactic body radiation therapy have gained an increasing interest in recent years and they have the potential to become the standard of care even if long-term data about their efficacy and safety are not well established. Strong radiobiological basis supports the use of high dose for fraction in prostate cancer, due to the demonstrated exceptionally low values of α/β. Clinical experiences with hypofractionated and stereotactic radiotherapy (with an adequate biologically equivalent dose) demonstrated good tolerance, a PSA control comparable to conventional fractionation, and the advantage of shorter time period of treatment. This paper reviews the radiobiological findings that have led to the increasing use of hypofractionation in the management of prostate cancer and briefly analyzes the clinical experience in this setting. [ABSTRACT FROM AUTHOR]

Background: The plasma concentration of endoxifen, the active metabolite of tamoxifen, might be affected by different CYP2D6 genotypes in patients with breast cancer, but solid evidence is still lacking in Asian patients. This prospective study aimed to investigate the relationship between CYP2D6 genetic polymorphisms and endoxifen plasma concentrations among Chinese patients with breast cancer treated with tamoxifen. Methods: From August 2015 to June 2018, 110 patients with breast cancer were enrolled. CYP2D6 variant alleles and endoxifen plasma concentration were determined using Sanger sequencing and high-performance liquid chromatography-tandem mass spectrometry, respectively. Results: The most frequent allele of CYP2D6 was *10 (56.4%). The most frequent genotype of CYP2D6 was *10/*10 (33%), *1/*10(28.2%) and *2/*10(14.5%). Sixty-four patients (58.2%) were Normal Metabolizers (NM), while 46 (41.8%) were Intermediate Metabolizers (IM). All patients except two had endoxifen concentrations above the threshold of 5.9ng/ml. The median endoxifen plasma concentrations for patients with CYP2D6 genotypes *1/*2 and *1/10 were higher compared to other genotypes (p = 0.012). The median endoxifen plasma concentration was higher in NM than in IM (18ng/ml vs. 13ng/ml, p = 0.0077). Patients with CYP2D6*10(T/T) had lower endoxifen concentrations than those with *10(C/T) and *10(C/C) but the difference was not significant. There were no significant differences in adverse events between patients in the NM and IM groups or between patients with the CYP2D6*10 (T/T) genotype and non-*10 (T/T) genotype. Conclusion: Only CYP2D6 IMs and NMs were identified in this study. Almost all patients had the endoxifen concentrations above the threshold. The endoxifen plasma concentration was lower in CYP2D6 IMs than in NMs, but these variants did not compromise the adverse effects of tamoxifen in Asian patients with breast cancer. Trial registration: The study protocol was approved by the institutional review boards of Sun YatSen University Cancer Center (Ethics approval number, B201506501,20160115). [ABSTRACT FROM AUTHOR]

Triple-positive breast cancer (TPBC), a unique subtype of luminal breast cancer, is characterized by concurrent positivity for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Owing to the crosstalk between the ER and HER2 signaling pathways, the standard of care and drug resistance of this particular subtype are difficult challenges. Recent research and clinical trials have indicated a shift in the treatment paradigm for TPBC from single-target therapies to multi-pathway, multitarget strategies aiming to comprehensively modulate intricate signaling networks, thereby overcoming resistance and enhancing therapeutic outcomes. Among multiple strategies, triple-drug therapy has emerged as a promising treatment modality, demonstrating potential efficacy in patients with TPBC. Moving forward, there is a critical need to perform in-depth analyses of specific mechanisms of cancer pathogenesis and metastasis, decipher the complex interactions between different genes or proteins, and identify concrete molecular targets, thus paving the way for the development of tailored therapeutic strategies to combat TPBC effectively. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to discover immune-nutritional indicators that can preoperatively predict short-term mortality in older patients undergoing emergency gastrointestinal surgery. Methods: We retrospectively analyzed older patients older than 65 years of age who underwent various types of emergency gastrointestinal surgery under general anesthesia between January 2012 and December 2023. The immune-nutritional indicators were defined according to previous literature. The primary endpoint of this study was 90-day survival after surgery. Results: A total of 4120 patients older than 65 years were included in this study. ROC curves and the decision curve analysis for eight factors predicting 90-day postoperative survival were well predicted by the mGPS (0.68, 95% CI: 0.66–0.70), PNI (0.68, 95% CI: 0.66–0.71) and CONUT score (0.68, 95% CI: 0.66–0.70). The models constructed by LASSO Cox and CoxBoost were used to score the risk for each patient, and the high LASSO Cox model risk score group had worse 90-day survival than the low score group, whereas patients in the low CoxBoost model score group had a worse prognosis. The AUC of the CoxBoost model was greater than that of the LASSO Cox model. A nomogram model was constructed using the variables screened by the LASSO Cox model with a C-index of 0.706. Conclusions: Immune-nutritional factors could be a favorable predictor for older patients undergoing emergency gastrointestinal surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: The omission of axillary surgery is gaining popularity in selected groups of breast cancer patients. On the other hand, the exceptional nodal responses to neoadjuvant chemotherapy and dual Her2 blockage in Her2-positive breast cancer patients opens the way to the question of whether we can omit axillary surgery in such a group of patients or at least in a certain subgroup. This study aimed to evaluate the lymph node pathological status after neoadjuvant therapy in Her2+ breast cancer patients and to highlight the variables that can predict a pathological complete nodal response so that it can be expected without the need for surgical axillary staging Background: This study aimed to evaluate the lymph node (LN) response in Her2-positive breast cancer patients who received neoadjuvant therapy (NAT) and to discuss if axillary staging can be omitted in these patients. Methods: This is a retrospective cohort study including patients with Her2+ breast cancer at our center from March 2022 to September 2023. Results: The study included 139 patients in the final analysis; 69.1% of the patients had HR+/Her2+ disease while 30.9% had HR−/Her2+ disease. Most of the included patients (129 patients = 92.8%) had initially node-positive or suspicious disease. A total of 112 patients (80.6%) showed clinically negative axillary LNs (cN0) after NAT. All of them showed pathologically node-negative disease. When comparing the pathological node-positive vs. -negative groups, the following was found to be statistically significant: degree of Her2 positivity, number of anti-Her2 cycles, pre- and post-neoadjuvant LN status, and primary tumor radiological and pathological response. Also, all T1 tumors before NAT showed negative LNs after NAT, but it was statistically non-significant. Conclusions: Axillary staging may be omitted in Her2+ patients with cN0 after NAT, especially those with early tumors, strong Her2+ disease, cN0 before NAT, and those in whom the primary tumor achieved a complete clinical response. [ABSTRACT FROM AUTHOR]

Background/Objective: Pressure ulcers represent a significant complication in patients with reduced mobility, such as those recovering from hip fractures. In the present study, we aimed to comprehensively assess the impact of oral nutritional interventions on the development of pressure ulcers in hip fracture patients via a systematic review and meta-analysis of controlled studies evaluating the effectiveness of oral nutritional supplements compared with standard care. Methods: In accordance with PRISMA standards, this systematic review and meta-analysis of controlled studies evaluated the effectiveness of any type of oral nutritional supplements compared with standard care in hip fracture patients. The risk of bias was evaluated using the Cochrane ROB2 tool for randomized controlled trials and the ROBINS-1 tool for nonrandomized trials. Results: Fourteen studies (10 randomized controlled trials and 4 controlled trials) published since 1990 (n = 1648) were included. Oral nutritional supplementation was associated with a statistically significant decrease in the odds ratio of developing pressure ulcers in hip fracture patients (OR 0.54, 95% CI: 0.40–0.73, p < 0.001). Conclusions: The incidence and evolution of pressure ulcers can be improved by oral dietary supplementation in patients who have undergone hip fracture surgery. Accordingly, we propose that oral nutritional supplementation should be considered an essential component of comprehensive post-hip-fracture care. [ABSTRACT FROM AUTHOR]

Simple Summary: T cell receptor fusion constructs (TRuC-Ts) represent a promising next-generation T cell therapy for solid tumors. To enhance their development, improved patient selection is essential. A pilot study was conducted to evaluate the feasibility and performance of a predictive model for treatment responses in mesothelioma patients, leveraging radiomics and machine learning. Radiomics and delta-radiomics (Δradiomics) features from CT scans were analyzed for reproducibility and informativeness, identifying key features for training a random forest classifier. The model achieved an accuracy of 0.75–0.9 in predicting pleural tumor responses, supporting the design of future studies involving 250–400 tumors. This study demonstrated the reproducibility and effectiveness of radiomics/Δradiomics in relation to tumor localization, emphasizing the need for multiple tumor models to create an integrated patient model. These findings provide a foundation for combining tumor-specific models into a unified approach, improving patient selection for TRuC-T therapy in mesothelioma patients. Background/Objectives: T cell receptor fusion constructs (TRuCs), a next generation engineered T cell therapy, hold great promise. To accelerate the clinical development of these therapies, improving patient selection is a crucial pathway forward. Methods: We retrospectively analyzed 23 mesothelioma patients (85 target tumors) treated in a phase 1/2 single arm clinical trial (NCT03907852). Five imaging sites were involved, the settings for the evaluations were Blinded Independent Central Reviews (BICRs) with double reads. The reproducibility of 3416 radiomics and delta-radiomics (Δradiomics) was assessed. The univariate analysis evaluated correlations at the target tumor level with (1) tumor diameter response; (2) tumor volume response, according to the Quantitative Imaging Biomarker Alliance; and (3) the mean standard uptake value (SUV) response, as defined by the positron emission tomography response criteria in solid tumors (PERCISTs). A random forest model predicted the response of the target pleural tumors. Results: Tumor anatomical distribution was 55.3%, 17.6%, 14.1%, and 10.6% in the pleura, lymph nodes, peritoneum, and soft tissues, respectively. Radiomics/Δradiomics reproducibility differed across tumor localizations. Radiomics were more reproducible than Δradiomics. In the univariate analysis, none of the radiomics/Δradiomics correlated with any response criteria. With an accuracy ranging from 0.75 to 0.9, three radiomics/Δradiomics were able to predict the response of target pleural tumors. Pivotal studies will require a sample size of 250 to 400 tumors. Conclusions: The prediction of responding target pleural tumors can be achieved using a machine learning-based radiomics/Δradiomics analysis. Tumor-specific reproducibility and the average values indicated that using tumor models to create an effective patient model would require combining several target tumor models. [ABSTRACT FROM AUTHOR]

Background/Objectives: The lung is the most common site of metastases, regardless of the cancer subtype. Treating oligometastatic disease with surgery or stereotactic ablative radiotherapy (SABR) may improve patient survival. Methods: We retrospectively analyzed 41 patients with limited (one or two lesions, max dimension <3 cm) lung-only metastatic disease that were treated with the CK M6 robotic radiosurgery system in our Department, in terms of treatment efficacy and toxicity. Results: Acute and late toxicity was negligible (4 out of 41 patients developed grade 2 or 3 lung fibrosis). Six months post-SABR, complete response was achieved in 18 out of 41 patients (43.9%), while the rest of the cases exhibited major responses. A biological effective dose (BEDα/β=10) in the range of 100 Gy appears to be equally effective with higher doses. Within a median follow-up of 34 months, only three patients (7.3%) progressed locally, while three patients progressed to distal sites. Two-year local progression-free survival (LPFS) rates were 92.6% (95% CI 78.5–97%). Conclusions: SABR for low-burden lung oligometastases is an effective treatment modality that yields high local control and survival rates. Toxicity is negligible, regardless of the performance status of patients. Early referral of such patients to radiation oncology departments may be critical for patient survival and quality of life. [ABSTRACT FROM AUTHOR]

Introduction: Malnutrition is a major contributor to poor treatment and survival outcomes in pancreatic cancer, yet nutritional assessment is not standardized or consistently implemented in the care of oncology patients. The Geriatric Nutritional Risk Index (GNRI), calculated from serum albumin and body weight, may be useful as a practical tool for identifying patients at risk of poor nutritional status. Purpose: To provide a preliminary analysis using a limited selection of variables to examine the association of the GNRI at diagnosis and the GNRI change over time with overall survival in patients with pancreatic cancer. Methods: This retrospective study included 314 patients aged ≥18 years with pancreatic cancer. The GNRI was calculated at diagnosis and ≥30 days later. Patients were categorized by the GNRI at diagnosis (no risk >98, any risk ≤98) and change in the GNRI over time (no change/increase, mild decrease, and severe decrease). Additional variables included were demographics and stage. Comparative analysis included t-tests, chi-square tests, and ANOVA. Survival was analyzed using Kaplan–Meier curves, log-rank tests, and Cox proportional hazards modeling. Results: Median survival was significantly decreased in patients in the any-nutritional-risk group compared to the no-nutritional-risk group at diagnosis (442 vs. 1105 days), and those experiencing severe decreases in the GNRI scores compared to mild decreases and no change or increases (372.5 vs. 712 vs. 1791 days), respectively. Survival analysis stratified by the GNRI at diagnosis shows that both mild (HR 2.19, 95%, and CI 1.46–3.30) and severe decreases (HR 4.04, 95%, and CI 2.64–6.18) in the GNRI scores were independently associated with decreased survival versus no change or increase in the GNRI group after controlling for stage. Log-rank tests also show patients with any nutritional risk at diagnosis had significantly lower survival than those with no nutritional risk (p = 0.00052). Conclusions: Lower GNRI scores showing greater nutritional risk at diagnosis and decreasing GNRI scores over time were predictors of decreased survival in pancreatic cancer. Our findings indicate that the GNRI may be valid and effective for the early identification of patients with a high nutritional risk who require nutritional interventions to improve outcomes in pancreatic cancer. However, more research is needed using larger samples and a greater variety of variables to confirm the presence and strength of this relationship, examine the effect of patient factors known to be associated with survival and nutrition, and explore potential influential confounders. [ABSTRACT FROM AUTHOR]

Background/Objectives: The most common type of breast cancer (BRC) in women is estrogen/progesterone receptor positive. First-line treatment includes endocrine therapy, either with aromatase inhibitors or tamoxifen to reduce estrogen levels. Among the side effects produced by this treatment, aromatase inhibitor-induced arthralgia is the most common, affecting the patients' overall health and quality of life (QoL). The objectives here were to evaluate interventions examining the impact of modified diets, supplements, and/or some food components on health outcomes in BRC patients undergoing endocrine therapy. Methods: The literature search was performed in PubMed, Scopus, and Web of Science from June 2024, as well as manually, through the end of November 2024. The search was limited to studies of women diagnosed with estrogen/progesterone-receptor-positive BRC with selected articles reporting interventions with diet, food, or supplement intake and examining the relevant health outcomes. Studies not focusing on BRC patients undergoing endocrine therapy or not including specific health outcomes were excluded. Results: The search uncovered 1028 studies; after the removal of duplicates, abstracts, and irrelevant studies, 53 were closely examined, with 26 evaluated and presented here. The outcomes were changes in bone and body composition, cardiovascular disease risks, inflammation, and QoL. Conclusions: The examined evidence suggests that adherence to dietary patterns such as the Mediterranean or a low-fat diet, and a higher intake of fruits and vegetables were beneficial for various outcomes. Additionally, supplementation with some foods/components (dried plum, red clover) contributed to improving/maintaining bone and body composition, especially in overweight/obese patients. Supplementation with vitamin D or omega-3 improved lipid and angiogenic parameters and QoL. Although these results are promising, the effects of each supplement/food cannot be summarized due to the diverse nature of study designs, patients, and supplement dosages. Further studies are needed to explore the effects of specific nutritional interventions (including the newest, like fasting-mimicking diets and whole-grain cereal diets) on various health outcomes in BRC survivors during endocrine therapy, and to derive universal recommendations. [ABSTRACT FROM AUTHOR]

The burden of invasive fungal infections (IFIs) is increasing worldwide. National, regional, and local policies on IFI management should respond to the changing landscape. We assessed antifungal policies from five countries of varying size, IFI burden, and geography: the Netherlands, Italy, South Korea, China, and India. These countries were selected as a representative sample reflecting different types of economic and health systems that patients and providers access worldwide. This assessment focused on a comprehensive range of antifungal policy elements, including recognition and prioritization, awareness and education, prevention and monitoring, diagnosis and coordinated care, access to appropriate treatment, and diagnostic and treatment innovation. Although countries in this analysis all have some form of policy for IFI management, we have identified substantial gaps, including low prioritization of IFI diagnostics, omission of fungal pathogens from antimicrobial resistance policies, and a general lack of awareness and healthcare professional (HCP) training on IFI management. The gaps identified are intended to inform HCPs and policy- and decision-makers about aspects to consider in reducing the IFI burden for patients and health systems while demonstrating responsible antifungal stewardship. [ABSTRACT FROM AUTHOR]

Introduction: Chemoradiation therapy (CRT) with concurrent high-dose cisplatin (CDDP) is one of the standard treatment options for locally advanced head and neck cancer. Since the indications specific to the older population have not been reported, we conducted a multicenter survey on the indications. Methods: In April and May 2023, a questionnaire survey was emailed to all institutions belonging to the JCOG-HNCSG, consisting of 37 institutions. Results: The major factors influencing the indications for high-dose CDDP were renal function and performance status (PS). The majority agreed that the treatment is administered to patients aged 65–74 years with PS 0–1 and 65–74 years with eGFR ≥60 (ml/ min/1.73m2), and not in patients aged ≥75 years with PS 2, ≥80 years with PS 1, and ≥65 years with eGFR <60. Regarding weekly CDDP, the majority agreed that the treatment is not conducted in patients aged ≥75 years with PS 2, ≥65 years with eGFR <40, and ≥70 years with eGFR <50. Discussion: In Japan, where CRT is actively performed even among older people, a survey was conducted to determine its indications. Renal function and PS were considered important, and comorbidities, such as heart failure, were considered while determining the indication. These results will help define the eligibility criteria for prospective studies on CRT in older patients. [ABSTRACT FROM AUTHOR]

The integration of deep learning (DL) into image processing has driven transformative advancements, enabling capabilities far beyond the reach of traditional methodologies. This survey offers an in-depth exploration of the DL approaches that have redefined image processing, tracing their evolution from early innovations to the latest state-of-the-art developments. It also analyzes the progression of architectural designs and learning paradigms that have significantly enhanced the ability to process and interpret complex visual data. Key advancements, such as techniques improving model efficiency, generalization, and robustness, are examined, showcasing DL's ability to address increasingly sophisticated image-processing tasks across diverse domains. Metrics used for rigorous model evaluation are also discussed, underscoring the importance of performance assessment in varied application contexts. The impact of DL in image processing is highlighted through its ability to tackle complex challenges and generate actionable insights. Finally, this survey identifies potential future directions, including the integration of emerging technologies like quantum computing and neuromorphic architectures for enhanced efficiency and federated learning for privacy-preserving training. Additionally, it highlights the potential of combining DL with emerging technologies such as edge computing and explainable artificial intelligence (AI) to address scalability and interpretability challenges. These advancements are positioned to further extend the capabilities and applications of DL, driving innovation in image processing. [ABSTRACT FROM AUTHOR]

Accelerated partial breast irradiation (APBI) represents a valid option for adjuvant therapy of selected early breast cancer (BC). This single-institution prospective randomized study compares the health-related quality of life (HRQoL) between women treated with the highly conformal-external beam APBI technique and those with the more commonly used moderately hypofractionated whole breast irradiation (hypo-WBI). Eligible patients were women over 50 years with early BC (G1/2 DCIS ≤ 25 mm or G1/2 invasive non-lobular luminal-like HER2 negative carcinoma ≤ 20 mm) after breast-conserving surgery with negative margins. APBI arm consisted of 30 Gy in 5 consecutive daily fractions and WBI arm of 40 Gy in 15 fractions plus 10 Gy in 5 fractions boost to the tumor bed. Patients were requested to complete the official Czech translation of the EORTC QoL questionnaires, including QLQ-C30 and QLQ-BR45, before radiation (baseline), at the end of radiation (M0) and 1 (M1), 3 (M3), 6 (M6), 12 (M12), and 24 (M24) months after radiation. Linear regression models were used to analyze differences in HRQoL between the arms. The 85 enrolled patients exhibited no differences in HRQoL scores between the two arms at baseline. Patients in the APBI arm reported more favorable global health status at M6 (p = 0.055). Other functional scales showed a decrease in the WBI arm at M0 (p = 0.027 for physical functioning). During radiation, symptoms scores increased. Significant between-group differences were observed for the pain (p = 0.002), systemic therapy side effects (p = 0.004), and breast symptoms (p < 0.001) scales at M0, with higher scores in the WBI arm. During follow-up, scores on symptoms scales returned to at least the baseline values. Early BC patients treated with APBI showed non-inferior short-term and late HRQoL outcomes compared to hypo-WBI. In addition to previous findings regarding toxicity, promising pain and breast symptoms results, suggest that APBI should be strongly considered as a treatment option for selected low-risk patients. Trial registration NCT06007118, August 23, 2023 (retrospectively registered). [ABSTRACT FROM AUTHOR]

The simultaneous occurrence of head and neck squamous carcinoma in two anatomical sites is rare, posing challenges in treatment selection. This paper presents a clinical case of concurrent hypopharyngeal carcinoma and nasopharyngeal carcinoma, successfully treated with a combination of chemoradiotherapy and an immune checkpoint inhibitor. The patient achieved complete remission and progression-free survival of nearly 3 years, with preserved organ function and minimal toxic side effects, leading to a good quality of life. This case highlights the potential of combined concurrent chemoradiotherapy and immune checkpoint inhibitors in managing double primary HNSCC, offering a promising treatment option for these patients. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to explore the role of the non-luminal disease score (NOLUS) for everolimus in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). Methods: NOLUS has previously been established as an algorithm: NOLUS (0– 100) = − 0.45 × ER(%) − 0.28 × PR(%) + 0.27 × Ki67(%) + 73. Information of cancer patients was retrospectively collected from three cancer centers in China. Results: Totally, 198 HR+/HER2- ABC patients with complete records in expression rates (%) of ER, PR and Ki67 were enrolled in the study. The expression rates (%) of ER, PR, and Ki67 were 38.8 ± 27.9 versus 80.9 ± 14.2 (p < 0.001), 13.9 ± 14.3 versus 50.2 ± 30.4 (p < 0.001), and 37.8 ± 23.6 versus 28.7 ± 19.9 (p = 0.04), respectively, for NOLUS-positive patients and NOLUS-negative patients. For the overall population, the median PFS was 5.8 months versus 5.1 months in NOLUS-positive and NOLUS-negative patients (p = 0.16, HR = 0.75, 95% CI = 0.50, 1.12). The median 1L-, 2L, and 3L-PFS was 13.9 months versus 11.8 months (p = 0.22, HR = 1.63, 95% CI = 0.74, 3.62), 6.7 months versus 3.6 months (p = 0.08, HR = 0.34, 95% CI = 0.10, 1.18), and 4.6 months versus 4.0 months (p = 0.81, HR = 1.07, 95% CI = 0.63, 1.79) respectively, for NOLUS-positive patients and NOLUS-negative patients. Conclusion: NOLUS-positive patients have a lower percentage of ER and PR, but a higher percentage of Ki67 index. The correlation between the benefits of everolimus and NOLUS failed to develop significance, suggesting that NOLUS may not be applicable in predicting everolimus efficacy in patients with HR+/HER2- ABC. Further research is expected. [ABSTRACT FROM AUTHOR]

Normal tissue reactions vary significantly among patients receiving the same radiation treatment regimen, reflecting the multifactorial etiology of late radiation toxicity. Predicting late radiation toxicity is crucial, as it aids in the initial decision-making process regarding the treatment modalities. For patients undergoing radiotherapy, anticipating late toxicity allows for planning adjustments to optimize individualized care. Various dosimetric parameters have been shown to influence the incidence of late toxicity, and the literature available on this topic is extensive. This narrative review examines patient-related determinants of late toxicity following external beam radiotherapy for pelvic tumors, with a focus on prostate and cervical cancer patients. In Part I, we address various methods for quantifying radiation toxicity, providing context for interpreting toxicity data. Part II examines the current insights into the clinical risk factors for late toxicity. While certain factors—such as previous abdominal surgery, smoking behavior, and severe acute toxicity—have consistently been reported, most of the others show inconsistent associations. In Part III, we explore the influence of genetic factors and discuss promising predictive assays. Single-nucleotide polymorphisms (SNPs) likely elevate the risk in specific combinations. Advances in artificial intelligence now allow for the identification of SNP patterns from large datasets, supporting the development of polygenic risk scores. These innovations hold promise for improving personalized treatment strategies and reducing the burden of late toxicity in cancer survivors. [ABSTRACT FROM AUTHOR]

Introduction: Temporo-insular gliomas, rare brain tumors originating from glial cells, comprise about 30% of brain tumors and vary in aggressiveness from grade I to IV. Despite advancements in neuroimaging and surgical techniques, their management remains complex due to their location near critical cognitive areas. Techniques like awake craniotomy have improved outcomes, but tumor heterogeneity and proximity to vital structures pose challenges. Radiotherapy and chemotherapy offer benefits post-surgery, though issues like resistance and side effects persist. This article discusses a case report and literature review to deepen understanding of temporo-insular gliomas, focusing on advanced diagnostic and treatment approaches. Materials and Methods: A systematic review was conducted using PubMed, Embase, and Google Scholar, covering studies from 2019 to July 2024. Keywords included 'brain tumor', 'neurosurgery', and 'treatment'. Articles on glioma diagnosis, management, and outcomes were selected, excluding non-English studies, irrelevant reports, non-glioma research, and inaccessible texts. Results: From 156 studies, 11 met inclusion criteria, highlighting advanced diagnostics, surgical strategies, and adjunct therapies for temporo-insular gliomas (TIGs). Gross total resection (GTR) was achieved in 39% of cases. Awake craniotomy enhanced functional outcomes, while temozolomide and radiotherapy improved survival. Challenges included ischemic complications and treatment resistance. Two patient cases underscored the complexity of TIG management and the importance of individualized approaches, achieving satisfactory resection with minimal deficits. Conclusions: Temporo-insular gliomas (TIGs) necessitate a multidisciplinary strategy that integrates advanced imaging, meticulous surgical methods, and cutting-edge adjuvant therapies. Despite progress with techniques like awake craniotomy and the use of temozolomide improving patient outcomes, significant challenges persist in maintaining functional integrity and addressing treatment resistance. Ongoing research into targeted therapies, immunotherapies, and innovative technologies remains critical to advancing patient care and improving long-term prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Nutritional care is a cornerstone of cancer treatment, with the potential to significantly improve patient outcomes by addressing malnutrition and enhancing recovery. Despite growing awareness, the integration of evidence-based nutritional strategies into oncology remains inconsistent. Following a 2020 survey that highlighted critical gaps, the NutriOnc Research Group launched targeted initiatives to raise awareness and improve practices. This study reassesses progress in integrating nutritional care and identifies persistent challenges. Methods: A 29-question survey was conducted in 2024 among 73 early-career oncologists, surgeons, radiation oncologists, and nutrition specialists across Italy. Respondents provided insights into clinical nutrition program availability, multidisciplinary team composition, screening practices, and educational needs. Results: Encouraging advancements were noted, with 80.8% of respondents reporting the presence of clinical nutrition programs, compared to fewer structured efforts in 2020. However, only 26.0% included nutrition specialists in multidisciplinary teams, and barriers such as financial constraints, limited product availability, and the absence of trained professionals persisted. While 82.2% performed nutritional screening, variability in tools and practices highlighted the need for standardization. Strikingly, 98.6% expressed a strong demand for advanced education on clinical nutrition, emphasizing the need for innovative and accessible training programs. Conclusions: This study reveals a landscape of progress tempered by persistent inequities. To close the gap, oncology must embrace standardized protocols, expand access to trained nutrition specialists, and invest in educational initiatives. The findings offer actionable insights for transforming cancer care through nutrition, underscoring its potential to improve survival, quality of life, and overall treatment success. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cancer, a leading cause of mortality globally and in Brazil, is influenced by environmental and behavioral factors, often linked to nutritional deficiencies such as low body mass index and muscle wasting, exacerbating prognostic outcomes and mortality rates. Timely nutritional interventions during chemotherapy are pivotal, necessitating continuous nutritional assessment for effective patient care management. This study aimed to assess the nutritional status of non-metastatic cancer patients undergoing chemotherapy and identify factors influencing their nutritional status. Patient evaluation involved sociodemographic data, clinical profiles, anthropometric measurements, blood biochemical analyses, and nutritional status classification employing the Patient-Generated Subjective Global Assessment (PG-SGA) criteria. Statistical analysis was performed using R software. Results: Suspected malnutrition was identified in 5.81% of patients, with a significant association observed with gender, indicating a higher prevalence among men. Cancer stages II and III, along with a positive family history, correlated with heightened risk of malnutrition. Patients with suspected malnutrition exhibited older age, lower weight, body mass index (BMI), and reduced circumferences, underscoring the necessity of comprehensive nutritional assessment for optimized patient management during treatment. Conclusions: This study underscores a notable prevalence of malnutrition, particularly among patients with lower weight and BMI, affirming the reliability of PG-SGA criteria. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most prevalent cancers worldwide. Recent studies have increasingly emphasized the role of oxidative stress in the initiation and progression of breast cancer. This article reviews how oxidative stress imbalance influences the occurrence and advancement of breast cancer, elucidating the intricate mechanisms through which reactive oxygen species (ROS) operate in this context and their potential therapeutic applications. By highlighting these critical insights, this review aims to enhance our understanding of oxidative stress as a potential target for innovative therapeutic strategies in the management of breast cancer. [ABSTRACT FROM AUTHOR]

Aims: To summarize the morphological characteristics and development and healing processes of severe radiodermatitis for examining the factors contributing to the development of severe radiodermatitis in patients with head and neck cancer. Methods: This scoping review was conducted in accordance with PRISMA extension for Scoping Reviews. Data were extracted from selected references describing detailed conditions of severe radiodermatitis in patients with head and neck cancer. The data were organized separately for radiotherapy, chemoradiotherapy, and bioradiotherapy. Data Sources: Medline, PubMed, CINAHL, and Cochrane Central Register of Controlled Trials databases were used to search for papers from 2000 to December 2023. Results: 11 out of 658 references met the criteria for this review. The morphological characteristics of severe radiodermatitis were categorized by symptoms, site, and shape, and a condition in which moist desquamations and associated crusts spreading to the anterior and lateral neck areas were extracted. In bioradiotherapy, the process of keratinocyte degeneration and formation of blisters under the epidermis leading to moist desquamations was extracted. In chemoradiotherapy, the process of epithelization was extracted 1 week following the occurrence of moist desquamations. Conclusions: Moist desquamations are more likely to occur in severe radiodermatitis in patients with head and neck cancer. Since they can fuse and spread, preventative measures to mitigate spreading are important. However, there is insufficient information to examine the causes of widespread moist desquamations. For preventing moist desquamations and establishing care methods to heal moist desquamations, it may be necessary to identify the symptoms, site, and shape, including the color tone and depth, and healing process during their occurrence. [ABSTRACT FROM AUTHOR]

Background: Many patients with head and neck cancer are not candidates for standard of care definitive treatments though often require palliative treatments given the frequent symptoms associated with head and neck cancer. While existing palliative radiotherapy regimens can provide adequate symptom control, they have limitations particularly with respect to local control which is becoming more important as advances in systemic therapy are improving survival. Personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR) is a novel radiotherapy regimen which leverages advances in radiotherapy treatment technology and extended interfraction intervals to enable adaptive radiotherapy and possible synergy with the immune system. Additionally, HyperArc© (Varian Medical Systems, Inc.) radiotherapy planning software allows for safe dose-escalation to head and neck tumors. Methods: This single-arm phase II study will prospectively evaluate PULSAR with HyperArc© software for palliative treatment of head and neck cancer. Patients with de novo or recurrent, localized or metastatic, head and neck cancer who are ineligible for or decline standard of care definitive treatments are eligible for enrollment. Forty-three patients will receive an 11 Gray fraction of radiation every two weeks for a total of five fractions and dose of 55 Gy. Adaptive radiotherapy planning is permitted. A safety and feasibility evaluation will be performed after enrollment of the first fifteen patients whereby the trial will be closed if five or more patients experience a CTCAEv5.0 grade 3 or 4 or any patient experiences a grade 5 toxicity probably attributable to PULSAR during or within three months after its completion. The primary endpoint is one-year local head and neck tumor control. Secondary endpoints include safety, disease progression-free and overall survival, symptomatic impact, frequency of re-simulation and/or adaptive planning, and radiation dosimetry of PULSAR. Additionally, enrolled patients are permitted to receive cancer-directed systemic therapy, including immunotherapy, during PULSAR which may allow for the analysis of the safety and efficacy of this combination. Discussion: The PULS-Pal trial is the first prospective study of PULSAR with HyperArc© software for head and neck cancer. We hypothesize that this radiotherapy regimen will lead to improved local tumor control compared with historical controls in patients undergoing palliative radiotherapy for head and neck cancer. Trial registration: Clinicaltrials.gov identifier: NCT06572423. Date of registration: August 28th, 2024. [ABSTRACT FROM AUTHOR]

Objective: The potential of immune-related adverse events (irAEs) in predicting the efficacy of PD-1 inhibitors in advanced non-small-cell lung cancer (NSCLC) has rarely been assessed. This study investigated the associations between irAEs and the clinical efficacy of PD-1 inhibitors combination therapy in patients with advanced NSCLC. Methods: A retrospective analysis was conducted of 73 patients with advanced NSCLC receiving PD-1 inhibitors combination therapy from January 2022 and July 2023. Patients were divided into two cohorts: patients with irAEs and patients without irAEs. We conducted an analysis to investigate the impact of irAEs on these different clinical outcomes. Results: There were no significant differences observed in clinical characteristics between the two cohorts, except for smoking status (P = 0.011).The cohort with irAEs exhibited a higher objective response rate (ORR) and disease control rate (DCR) compared to the cohort without irAEs (ORR: 32.5% vs 12.1%, P = 0.040; DCR: 80.0% vs 48.5%, P = 0.010).Moreover, the median progression-free survival (PFS) and overall survival (OS) were significantly better in the cohort with irAEs compared to the cohort without irAEs (PFS: 12.4 months vs 6.8 months, P = 0.009; OS: not reached vs 18.3 months, P = 0.024). Additionally, the multivariate COX regression analysis revealed that mild irAEs (PFS: HR = 0.386, 95% CI: 0.199–0.748, P = 0.005; OS: HR = 0.300, 95% CI: 0.105–0.855, P = 0.024) and single-system irAEs (PFS: HR = 0.401, 95% CI: 0.208–0.772, P = 0.006; OS: HR = 0.264, 95% CI: 0.090–0.776, P = 0.015) were identified as independent prognostic factors for both PFS and OS. Conclusions: IrAEs, especially thyroid irAEs, as well as mild or single-system irAEs, may serve as predictors of improved efficacy in advanced NSCLC patients receiving PD-1 inhibitors combination therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: The objective of the present systematic review was to evaluate the clinical outcomes and toxicity of the use of hypofractionation in adjuvant/salvage prostate cancer treatments. A total of 139 studies were identified and, finally, 33 studies were included in our analysis, with a total number of 4269 patients. Biochemical relapse-free survival (bRFS) ranged between 85% and 91% at 3 years, and between 47% and 78.6% at 5 years. Genitourinary (GU) and gastrointestinal (GI) acute toxicity was mild to moderate with comparable rates across the studies. Although some doubts remain on late toxic effects, hypofractionated treatment has been shown to be safe, effective, with moderate toxicity and not inferior to conventional RT, with good biochemical control rates. Background: Radical prostatectomy (RP) is one possible curative treatment for localized prostate cancer. Despite that, up to 40% of patients will later relapse. Currently, post-operative radiotherapy (PORT) courses deliver 1.8–2 Gy daily to reach a total dose ranging between 64 and 74 Gy, completed in 7–8 weeks. Several articles reported encouraging data in terms of the effectiveness and the related toxicities using hypofractionation schedules. The objective of the present systematic review was to evaluate the clinical outcomes and toxicity of the use of hypofractionation in adjuvant/salvage prostate cancer treatments. Methods: Medline was searched via PubMed and Scopus from inception to July 2024 to retrieve studies on hypofractionation in adjuvant/salvage prostate cancer treatments. This study was conducted under PRISMA guidelines. Results: A total of 139 articles were identified from the initial search. Subsequently, the 139 studies were reviewed by title and abstract. Ninety-five studies were excluded due to being either abstracts or articles not available in English. In the second step, the full texts of 44 studies were reviewed. Eleven studies were excluded for being reviews, study protocols, or focused on SBRT treatments. Finally, 33 studies were included in our analysis, with a total number of 4269 patients. Of the 33 selected studies, 20 were retrospective trials and 11 were phase I/II prospective trials, while 2 studies were prospective phase III trials. The follow-up ranged from 18 to 217 months. Failure-free survival, for those with the longer follow-up, ranged between 85% and 91% at 3 years, 47 and 78.6% at 5 years and 51.5% at 10 years. Genitourinary (GU) and gastrointestinal acute toxicity was mild to moderate with similar rates across the normofractionated and hypofractionated groups. Acute grade-3 GU toxicity events were unusual, occurring in less than 4% of the cases overall. Conclusion: The present study is the first systematic review of the literature that includes the first two randomized phase III studies published in the literature. Hypofractionated treatment has been shown to be safe, effective, with moderate toxicity and not inferior to conventional RT, with good biochemical control rates. [ABSTRACT FROM AUTHOR]

Simple Summary: Data are lacking on the optimal neoadjuvant systemic treatment of patients with hormone receptor and HER2 positive breast cancer who are unfit for the combination of chemotherapy and anti-HER2 therapy. A nationwide series of 190 breast cancer patients treated with neoadjuvant endocrine treatment (NET) or NET+anti-HER2 were evaluated. The ypT0 rate was significantly higher after NET+anti-HER2, with 10.0% (4/40) versus 1.3% (2/150) following NET (p = 0.019). The ypN0 rate was significantly higher after NET+anti-HER2, with 25.0% (6/24) versus 5.5% (3/55) following NET in cN+ patients (p = 0.020) and 81.3% (13/16) versus 55.8% (53/95) after NET in cN- patients (p = 0.047). In cN- patients, ypN0 status was independently associated with age (p = 0.008) and administration of NET+anti-HER2 (p = 0.016). These findings suggest a clinical benefit of treatment with NET+anti-HER2 if patients are unfit for the combination of anti-HER2 therapy with chemotherapy. Introduction: Data are lacking on the optimal neoadjuvant systemic treatment (NST) for women with hormone receptor-positive (HR+) human epidermal growth factor receptor 2-positive (HER2+) breast cancer if they are unfit to receive the combination of chemotherapy and anti-HER2 therapy. The aim of this study was to determine whether the rates of ypT0 and ypN0 differ between patients treated with neoadjuvant endocrine therapy (NET) versus NET combined with anti-HER2 therapy (NET+aHER2). Materials and Methods: Data from the Netherlands Cancer Registry were analysed to identify women diagnosed with primary HR+/HER2+ breast cancer between 2008 and 2019, treated with either NET or NET+aHER2. The ypT0 and ypN0 rates were analysed (using uni- and multivariable logistic regression analyses, as applicable) in relation to the characteristics of the patient, the tumour, and the treatment. Results: Of the 190 patients identified (median age 77), 150 had been treated with NET and 40 with NET+aHER2. Patients with clinically node-positive disease (cN+) were significantly more likely to have been treated with NET+aHER2 (p = 0.029). The ypT0 rate was significantly higher after NET+aHER2, with 10.0% (4/40) versus 1.3% (2/150) following NET (p = 0.019). The ypN0 rate was significantly higher after NET+aHER2, with 25.0% (6/24) versus 5.5% (3/55) following NET in the cN+ patients (p = 0.020) and 81.3% (13/16) versus 55.8% (53/95) after NET in the cN- patients (p = 0.047). In the cN- patients, the ypN0 status was independently associated with age (p = 0.008) and the administration of NET+aHER2 (p = 0.016). Conclusions: The rates of ypT0 and ypN0 in women with HR+/HER2+ breast cancer treated with NST was significantly higher following NET+aHER2 than after NET. [ABSTRACT FROM AUTHOR]

Smokeless tobacco (ST) is an alternative to smoking, which involves not the burning of tobacco. Although ST has been used for thousands of years, its health effects are not well characterized, and it is the subject of misconceptions throughout society. Therefore, it is crucial to identify the risks associated with ST use. We conducted a comprehensive search of the scientific literature to identify studies reporting associations between tobacco chewing and the risk of oral cancer and premalignant lesions. Our review discusses the molecular mechanisms associated with ST components, along with the role of ST use in speech impairment and cancer progression. We also examine the effectiveness of tobacco cessation strategies and review the existing perceptions held by ST consumers. Our findings indicate significant health risks associated with ST use, including increased cancer risk and speech impairments. As societal perceptions and misconceptions about ST are important factors that influence its use, there is a need for comprehensive public awareness campaigns to correct these misconceptions and to promote healthier lifestyle choices. We call for further research to improve cessation interventions and to increase public awareness of relevant research discoveries. By providing a thorough discussion of the health impacts of ST, we aim to inform policy decisions and public health strategies to reduce the prevalence of ST use. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma (HNSCC) is a common cancer in older adults, but treatment decisions for these patients can be challenging due to age-related factors, such as frailty. This study aimed to evaluate how pre-treatment frailty assessment can help predict survival outcomes and treatment-related side effects in older patients with HNSCC who undergo radiotherapy, with or without chemotherapy. We found that frailty plays a significant role in determining overall survival, but it was not directly related to acute radiation toxicity. Our findings suggest that incorporating frailty assessment into treatment planning could help personalize therapy for older patients, improving decision-making and potentially enhancing long-term outcomes. Background/Objectives: Over 60% of diagnoses of head and neck squamous cell carcinoma (HNSCC) occur in patients aged over 65. The benefits of radiotherapy (RT) combined with chemotherapy remain controversial in geriatric patients. Frailty stratification is underutilized in clinical practice despite evidence suggesting its predictive power. We aimed to assess the impact of pre-treatment frailty stratification on overall survival (OS) and acute radiation-related toxicity in a cohort of older patients with HNSCC. Methods: A prospective cohort of 117 patients aged ≥65 years with newly diagnosed HNSCC was enrolled between 2017 and 2022. Patients received RT with or without chemotherapy. Frailty was assessed using the 40-item Frailty Index (FI) as part of a comprehensive geriatric assessment. The primary outcomes were OS and acute RT toxicity, defined as a grade ≥ 3 based on CTCAE 5.0. Cox proportional hazard models and logistic regression models, adjusted for age, tumor stage, and chemotherapy, were used. Results: After a median follow-up of 819 days, FI (HR 1.478, 95% CI 1.182–1.848, p < 0.001) was an independent predictor of OS. Grade ≥ 3 toxicities were observed in 38% of patients, but frailty was not significantly associated with toxicity. A sub-analysis of oropharyngeal carcinoma patients demonstrated improved OS in HPV-positive patients (HR 0.231, 95% CI 0.078–0.686, p = 0.008). Conclusions: the standardized introduction of frailty assessment in the evaluation of older HNSCC patients holds great promise for predicting long-term survival. This approach could be crucial in tailoring treatment protocols that account for the biological heterogeneity of older adults. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is the second most common cancer in men, and radiotherapy (RT) is one of the main treatment options. Although effective, RT can cause toxic side effects. The accurate prediction of dosimetric parameters, enhanced by advanced technologies and AI-based predictive models, is crucial to optimize treatments and reduce toxicity risks. This study aims to explore current methodologies for predictive dosimetric parameters associated with RT toxicity in PCa patients, analyzing both traditional techniques and recent innovations. Methods: A systematic review was conducted using the PubMed, Scopus, and Medline databases to identify dosimetric predictive parameters for RT in prostate cancer. Studies published from 1987 to April 2024 were included, focusing on predictive models, dosimetric data, and AI techniques. Data extraction covered study details, methodology, predictive models, and results, with an emphasis on identifying trends and gaps in the research. Results: After removing duplicate manuscripts, 354 articles were identified from three databases, with 49 shortlisted for in-depth analysis. Of these, 27 met the inclusion criteria. Most studies utilized logistic regression models to analyze correlations between dosimetric parameters and toxicity, with the accuracy assessed by the area under the curve (AUC). The dosimetric parameter studies included Vdose, Dmax, and Dmean for the rectum, anal canal, bowel, and bladder. The evaluated toxicities were genitourinary, hematological, and gastrointestinal. Conclusions: Understanding dosimetric parameters, such as DVH, Dmax, and Dmean, is crucial for optimizing RT and predicting toxicity. Enhanced predictive accuracy improves treatment effectiveness and reduces side effects, ultimately improving patients' quality of life. Emerging artificial intelligence and machine learning technologies offer the potential to further refine RT in PCa by analyzing complex data, and enabling more personalized treatment approaches. [ABSTRACT FROM AUTHOR]

Background and Aims: Malnutrition is common in acutely ill geriatric patients, worsening immune function and clinical outcomes. Immunonutrition, containing nutrients like omega-3 fatty acids, arginin and glutamine, may improve recovery in this population. This study aimed to evaluate the impact of immunonutrition on clinical outcomes, inflammatory markers, and immune responses in frail, hospitalized older adults. Methods: This is a retrospective observational study. In total, 36 subjects, during hospitalization, received either an immunonutrition formula or isoproteic and isocaloric enteral nutrition. The primary outcome was the length of hospital stay (LOS), with secondary outcomes focused on inflammatory cytokines and immune parameters within a week of hospitalization. Results: Patients were primarily oldest-old, with a mean age of 88.6 years ± 4.9 (range 79–96). The immunonutrition group had a significantly shorter LOS (11.37 ± 4.87 vs. 16.82 ± 10.83 days, p = 0.05) and showed increases in key cytokines (G-CSF, INF-α2, IL-12p70, IL-15, IL-2, and IL-3, p < 0.05) enhanced immune function. A decrease in T cells and an increased B/T cell ratio was also observed. No significant differences in infection rates or 90-day survival were found. Conclusions: Enteral immunonutrition improved clinical outcomes by reducing LOS and modulating immune responses in frail patients, suggesting potential benefits in recovery. Further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Introduction: Cancer remains a leading cause of death globally, with patients frequently experiencing malnutrition due to both the disease and its treatment, which negatively affects their quality of life and treatment outcomes. Oral nutritional supplements (ONS) provide a noninvasive solution to improve nutritional status, but poor patient adherence limits their effectiveness. Studies on ONS adherence vary in their definitions and assessment tools, creating inconsistencies. A scoping review is essential to synthesize these studies and establish a foundation for future research and clinical practice. Method: We systematically searched six databases, including Web of Science, PubMed, and Scopus, up to August 2024. Our criteria focused on oncology patients, ONS interventions, and outcomes related to adherence definitions, assessment methods, and adherence rates. Results: 37 studies from 2005 to 2024 met the inclusion criteria. Definitions of ONS adherence and assessment methods vary widely, with the most common definition being the ratio of actual intake to the recommended amount. The assessment tools included self-reported ONS diaries, and MMAS scores, among others. Adherence rates also vary significantly, with some studies reporting a decline in adherence over time. Conclusion: The lack of standardized definitions and assessment methods for ONS adherence across studies hinders comparability. Future research should focus on developing standardized, comprehensive adherence assessment tools that incorporate both quantitative and qualitative data. This would allow for a better understanding of adherence factors and enable more targeted interventions to improve long-term adherence in cancer patients. [ABSTRACT FROM AUTHOR]

Glioblastoma is considered the most aggressive tumor of the central nervous system. The tumor microenvironment includes several components, such as endothelial cells, immune cells, and extracellular matrix components like matrix metalloproteinase-9 (MMP-9), which facilitates the proliferation of endothelial cells with pro-angiogenic roles. The MRI characteristics of glioblastomas can contribute to determining the prognosis. The aim of this study was to analyze the relationship between tumor angiogenesis in glioblastomas in association with MMP-9 immunoexpression. The results were correlated with the Ki-67 proliferation index, p53 immunoexpression, and the mutational status of IDH1 and ATRX, as well as MRI imaging data. This retrospective study included forty-four patients diagnosed with glioblastoma at the Department of Pathology, Târgu Mureș County Emergency Clinical Hospital. MMP-9 immunoexpression was observed in approximately half of the cases, more frequently in patients over 65 years old. Comparing the imaging data with the immunohistochemical results, we observed that the median tumor volume was higher in glioblastomas with IDH1 and p53 mutations, ATRX wild-type status, negative MMP-9 expression, and high Ki-67 proliferation indexes. The median values of MVD-CD34 and MVD-CD105 were higher in cases with extensive peritumoral edema in the contralateral hemisphere. Additionally, ATRX mutations were frequently associated with a more pronounced deviation of the median structures. To statistically validate the associations between MRI and the histopathological features of glioblastomas, further studies with larger cohorts are required. [ABSTRACT FROM AUTHOR]

HER2-positive (HER2+) breast cancer is characterized by the overexpression of the ERBB2 (HER2) gene, which promotes aggressive tumor growth and poor prognosis. Targeting the ERBB2 pathway with single-agent therapies has shown limited efficacy due to resistance mechanisms and the complexity of gene interactions within the tumor microenvironment. This study aims to explore potential drug synergies by analyzing gene–drug interactions and combination therapies that target the ERBB2 pathway in HER2+ breast tumors. Using gene co-expression network analysis, we identified 23 metabolic pathways with significant cross-linking of gene interactions, including those involving EGFR tyrosine kinase inhibitors, PI3K, mTOR, and others. We visualized these interactions using Cytoscape to generate individual and combined drug–gene networks, focusing on frequently used drugs such as Erlotinib, Gefitinib, Lapatinib, and Cetuximab. Individual networks highlighted the direct effects of these drugs on their target genes and neighboring genes within the ERBB2 pathway. Combined drug networks, such as those for Cetuximab with Lapatinib, Cetuximab with Erlotinib, and Erlotinib with Lapatinib, revealed potential synergies that could enhance therapeutic efficacy by simultaneously influencing multiple genes and pathways. Our findings suggest that a network-based approach to analyzing drug combinations provides valuable insights into the molecular mechanisms of HER2+ breast cancer and offers promising strategies for overcoming drug resistance and improving treatment outcomes. [ABSTRACT FROM AUTHOR]

Urological cancers including those of the prostate, bladder, and kidney, are prevalent and often lethal malignancies besides other less common ones like testicular and penile cancers. Current treatments have major limitations like side effects, recurrence, resistance, high costs, and poor quality of life. Nanotechnology offers promising solutions through enhanced diagnostic accuracy, targeted drug delivery, controlled release, and multimodal imaging. This review reflects clinical challenges and nanomedical advances across major urological cancers. In prostate cancer, nanoparticles improve delineation and radiosensitization in radiation therapy, enable fluorescent guidance in surgery, and enhance chemotherapy penetration in metastatic disease. Nanoparticles also overcome bladder permeability barriers to increase the residence time of intravesical therapy and chemotherapy agents. In renal cancer, nanocarriers potentiate tyrosine kinase inhibitors and immunotherapy while gene vectors and zinc oxide nanoparticles demonstrate antiproliferative effects. Across modalities, urological applications of nanomedicine include polymeric, liposomal, and metal nanoparticles for targeted therapy, prodrug delivery, photodynamic therapy, and thermal ablation. Biosafety assessments reveal favorable profiles but clinical translation remains limited, necessitating further trials. In conclusion, nanotechnology holds significant potential for earlier detection, precise intervention, and tailored treatment of urological malignancies, warranting expanded research to transform patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Nodes are the second site for prostate cancer recurrence. Whole-pelvic radiotherapy (WPRT) has shown superiority over nodal stereotactic body radiotherapy (SBRT) in two retrospective cohorts. We aimed to compare both modalities and assess factors associated with treatment outcomes. Materials and methods: This retrospective multicentric cohort study included patients from five institutions spanning from 2010 to 2022. Patients had a history of prostatic adenocarcinoma classified as N0 M0 at diagnosis with a first nodal-only pelvic castration-sensitive recurrence. Failure-free survival (FFS) was defined as the time from the end of RT to the first failure event–biochemical or imaging recurrence, or death. Results: A total of 147 patients (pts) were analyzed, mainly treated for a recurrence after initial prostatectomy (87%), with 64 (43.5%) undergoing SBRT and 83 (56.5%) undergoing WPRT. SBRT was chosen mainly for dosimetric constraints (67%) and was associated with a lower rate of concomitant androgen deprivation therapy (ADT) prescription. With a median follow-up of 68 months [inter-quartile range (IQR) = 51], FFS was significantly lower in the SBRT group (p < 0.0001). In multivariable analysis, WPRT and ADT were associated with a longer FFS. Factors associated with a longer FFS after SBRT included associated ADT, lower prostate-specific antigen (PSA) levels, a PSA doubling time >6 months, and a Gleason score <8. SBRT was associated with a lower rate of genitourinary and gastrointestinal grade ≥2 complications. Discussion: For an isolated pelvic nodal prostate cancer recurrence, SBRT is associated with a shorter FFS compared to WPRT. SBRT is often more convenient for patients and leaves further pelvic salvage options available, so it can be explored as an option for well-informed patients. [ABSTRACT FROM AUTHOR]

Head and neck cancer represents the seventh most common neoplasm worldwide, with squamous cell carcinoma being the most represented histologic variant. The rising incidence of the neoplastic pathology of this district, coupled with the drastic changes in its epidemiology over the past decades, have posed significant challenges to physicians worldwide in terms of diagnosis, prognosis, and treatment. In order to meet these challenges, a considerable amount of effort has been spent by the authors of the recent literature to explore new technologies and their possible employment for the better diagnostic and prognostic definition of head and neck squamous cell carcinoma (HNSCC). Among these technologies, a growing interest has been gathering around the possible applications of dual-energy computed tomography (DECT) in head and neck pathology. Dual-energy computed tomography (DECT) utilizes two distinct X-ray energy spectra to obtain two datasets in a single scan, allowing for material differentiation based on unique attenuation profiles. DECT offers key benefits such as enhanced contrast resolution, reduced beam-hardening artifacts, and precise iodine quantification through monochromatic reconstructions. It also creates material decomposition images, like iodine maps, aiding in tumor characterization and therapy assessment. This paper aims to summarize recent findings on the use of DECT in HNSCC, providing a comprehensive overview to aid further research and exploration in the field. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal squamous cell carcinoma (OPSCC) and its treatments often result in dysphagia, necessitating prolonged use of a nasogastric (NG) tube. NG tube removal rates in patients with OPSCC were compared between two strategies (induction chemotherapy followed by surgery versus induction chemotherapy followed by chemoradiation therapy). The outcomes related to swallowing function and NG tube dependence were shared with clinical physicians for guidance. Objectives: This retrospective observational study investigated to determine whether surgery or chemoradiation therapy after induction chemotherapy leads to better swallow function for oropharyngeal cancer patients. Methods: We documented the treatment paths and results of 267 patients with oropharyngeal squamous cell cancer (OPSCC). By quantifying nasogastric (NG) tube usage, surgery after induction chemotherapy (IC–surgery), and chemoradiation therapy after induction chemotherapy (IC-CRT) could be compared to determine the effectiveness of each. Cancer stages were also recorded concerning treatment options. The differences in NG tube usage IC–surgery and IC-CRT groups were compared. The NG tube dependence rates were also presented. Results: The prognosis and tube dependence differed significantly between the two groups. The IC–surgery had a better prognosis compared to IC-CRT for oropharyngeal cancer. The findings indicated that NG tube dependence was greater in advanced tumor stage 4 compared to stages 1–3, and NG tube dependence rates were higher for patients who underwent chemoradiation therapy after induction chemotherapy. Swallowing function was better in the IC–surgery group compared to the IC-CRT group. Conclusions: Higher NG tube retention rates and NG dependence are found in OPSCC patients who choose CRT as their treatment and also in the advanced-stage group. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer treatments like radiotherapy can sometimes cause tumors to shrink not only in the treated area but also in other parts of the body. This phenomenon, called the abscopal effect, happens when the immune system is triggered to attack tumors at distant sites. This review explores how heating the body (hyperthermia) alongside radiotherapy may improve the likelihood of this effect. Both treatments work by sending "danger" signals to the immune system, helping it recognize and attack cancer cells. Radiotherapy and hyperthermia together increase immune activity by releasing specific proteins and improving blood flow to the tumor, making it easier for immune cells to reach and attack cancer cells. This combination may offer a promising way to boost the body's natural defenses against cancer, helping more people experience widespread tumor shrinkage and potentially improving cancer treatment outcomes. Introduction: The abscopal effect is a systemic immune response characterized by metastases regression at sites distant from the irradiated lesion. This systematic review aims to explore the immunological mechanisms of action underlying the abscopal effect and to investigate how hyperthermia (HT) can increase the chances of radiotherapy (RT) triggering systemic anti-tumor immune responses. Methods: This review is created in accordance with the PRISMA guidelines. Results and Conclusion: HT and RT have both complementary and synergistic immunological effects. Both methods trigger danger signal release, promoting cytokine and chemokine secretion, which increases T-cell infiltration and facilitates cell death. Both treatments upregulate extracellular tumor HSP70, which could amplify DAMP recognition by macrophages and DCs, leading to stronger tumor antigen presentation and CTL-mediated immune responses. Additionally, the combined increase in cell adhesion molecules (VCAM-1, ICAM-1, E-selectin, L-selectin) could enhance leukocyte adhesion to tumors, improving lymphocyte trafficking and boosting systemic anti-tumor effects. Lastly, HT causes vasodilation and improves blood flow, which might exacerbate those distant effects. We suggest the combination of local radiotherapy with fever-range whole-body hyperthermia to optimally enhance the chances of triggering the abscopal effect mediated by the immune system. [ABSTRACT FROM AUTHOR]

Simple Summary: In this single-center retrospective analysis of 101 patients with recurrent glioblastoma, we demonstrate the benefit of a multimodal treatment approach with normo-fractionated re-RT with combined alkylating chemotherapy after surgical resection. Additionally, questions of patient selection, treatment tolerability, and patterns of relapse are addressed. Multimodal Treatment with re-resection followed by re-irradiation in combination with alkylating chemotherapy achieved the best results, especially when a combination of two agents (TMZ and CCNU) is used. Treatment was tolerated well with little evidence of radionecrosis or hematological toxicity and mean overall survival was 11.3 months (mean progression free survival: 9.5 months). No influence of second-line chemotherapy on patterns of relapse was detected. Background: Glioblastoma is the most common malignant brain tumor in adults. Even after maximal safe resection and adjuvant chemoradiotherapy, patients normally relapse after a few years or even months. Standard treatment for recurrent glioblastoma is not yet defined, with re-resection, re-irradiation, and systemic therapy playing key roles. Usually, re-irradiation is combined with concurrent chemotherapy, harnessing the radiosensitizing effects of alkylating agents. Methods: A retrospective analysis of 101 patients with recurrent glioblastoma treated with re-irradiation was conducted, evaluating the survival impact of concurrent chemotherapy regimens, as well as prior resection. Patients were subcategorized according to concurrent chemotherapy (temozolomide vs. CCNU vs. combination of both vs. none) and details are given regarding treatment toxicity and patterns of relapse after first- and second-line treatment. Results: Patients were treated with normo-fractionated re-irradiation (with prescription dose of ~40 Gy to the PTV), resulting in a moderate cumulative EQD2 (~100 Gy). The mean overall survival was 11.3 months (33.5 months from initial diagnosis) and mean progression free survival was 9.5 months. Prior resection resulted in increased survival (p < 0.001), especially when gross total resection was achieved. Patients who received concurrent chemotherapy had significantly longer survival vs. no chemotherapy (p < 0.01), with the combination of CCNU and TMZ achieving the best results. Overall survival was significantly better in patients who received the CCNU + TMZ combination at any time during treatment (first or second line) vs. monotherapy only. The treatment of larger volumes (mean PTV size = 112.7 cm3) was safe and did not result in worse prognosis or increased demand for corticosteroids. Overall, the incidence of high-grade toxicity or sequential radionecrosis (5%) was reasonably low and treatment was tolerated well. While second-line chemotherapy did not seem to influence patterns of relapse, patients who received TMZ + CCNU as first-line treatment had a tendency towards better local control with more out-field recurrence. Conclusions: Normo-fractionated re-irradiation appears to be safe and is accompanied by good survival outcomes, even when applied to larger treatment volumes. Patients amenable to undergo re-resection and achieving concurrent systemic therapy with alkylating agents had better OS, especially when gross total resection was possible. Based on existing data and experiences reflected in this analysis, we advocate for a multimodal approach to recurrent glioblastoma with maximal safe re-resection and adjuvant second chemoradiation. The combination of TMZ and CCNU for patients with methylated MGMT promoter yielded the best results in the primary and recurrent situation (together with re-RT). Normo-fractionated RT enables the use of more generous margins and is tolerated well. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, a syndrome characterized by age-related loss of muscle mass and function, lacks universally accepted diagnostic criteria, particularly for its role as a prognostic factor in elderly patients with non-small-cell lung cancer (NSCLC). This study aimed to evaluate the prognostic significance of sarcopenia, assessed by psoas muscle size on baseline CT scans, in patients over 70 years of age with metastatic NSCLC. Methods: We retrospectively analyzed 85 elderly patients undergoing palliative radiation therapy between August 2022 and July 2024. Using morphometric analysis of psoas size, we investigated its correlation with overall survival (OS) and progression-free survival (PFS). Results: Our results showed that decreased psoas size was significantly associated with shorter OS and PFS, with median OS of 10 months and PFS of 4 months in sarcopenic patients compared to longer survival times in non-sarcopenic patients. Median survival of non-sarcopenic vs. sarcopenic patients was 21 ± 7 months (muscle area > median) versus 5 ± 2.3 months (muscle area < median). Multivariate analysis confirmed that psoas size, along with ECOG performance status and treatment of primary NSCLC, was a significant predictor of survival. Discussion: These findings suggest that psoas muscle size is a valuable prognostic marker for elderly NSCLC patients, potentially guiding treatment decisions and patient management. Further research is needed to validate these results and refine prognostic models for this population. [ABSTRACT FROM AUTHOR]

Background and purpose: Differentiating high-grade gliomas (HGGs) from solitary brain metastases (SBMs) using conventional magnetic resonance imaging (MRI) remains challenging due to their similar imaging features. This study aimed to evaluate the diagnostic performance of advanced diffusion models, such as neurite orientation dispersion and density imaging (NODDI) and mean apparent propagator magnetic resonance imaging (MAP-MRI), in comparison to traditional techniques like diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DKI) for distinguishing HGGs from SBMs. Methods: In total, 17 patients with HGGs and 26 patients with SBMs were prospectively recruited based on the established inclusion and exclusion criteria. Structural MRI sequences and diffusion spectrum imaging (DSI) were utilized to assess quantitative parameter models, including NODDI, MAP-MRI, DWI, DTI, and DKI. Quantitative parameters were measured for both the tumor parenchymal area and the peritumoral edema area. The quantitative parameters of the two patient groups were compared using either the independent Student's t-test or the Mann--Whitney U test. The effectiveness of each model was evaluated using receiver operating characteristic (ROC) curves and calculating the area under the curve (AUC). Finally, the DeLong test was employed to compare the diagnostic performance of each model through pairwise comparisons of ROC curves. Results: Isotropic volume fraction (Viso) based on NODDI; mean squared displacement (MSD) and the return to plane probabilities (RTPP) based on MAP-MRI; radial diffusivity (RDk) and mean diffusivity (MDk) based on DKI; and axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) based on DTI of the peritumoral edema tumor were significantly different between HGGs and SBMs (p < 0.05). The optimal single discriminant parameters for each model are NODDI_Viso, MAP-MRI_MSD, DKI_MDk, and DTI_AD. Among these, the AUC of Viso (0.809) exceeds that of MSD (0.733), MDk (0.718), and AD (0.779). The combined model, which incorporates DTI_AD, DKI_RD, and NODDI_Viso, demonstrated superior diagnostic performance (0.897). Conclusions: Advanced diffusion MRI quantitative parameters derived from NODDI, such as Viso, have the potential to enhance the differentiation between HGGs and SBMs. The integrated utilization of these models is anticipated to enhance diagnostic accuracy and refine MRI protocols for brain tumor assessment. [ABSTRACT FROM AUTHOR]

Glioblastoma remains the most prevalent and aggressive primary malignant brain tumor in adults, characterized by limited treatment options and a poor prognosis. Previous drug repurposing efforts have yielded only marginal survival benefits, particularly those involving inhibitors targeting receptor tyrosine kinase and cyclin-dependent kinase-retinoblastoma pathways. This limited efficacy is likely due to several critical challenges, including the tumor's molecular heterogeneity, the dynamic evolution of its genetic profile, and the restrictive nature of the blood-brain barrier that impedes effective drug delivery. Emerging diagnostic tools, such as circulating tumor DNA and extracellular vesicles, offer promising non-invasive methods for real-time tumor monitoring, potentially enabling the application of targeted therapies to more selected patient populations. Moreover, innovative drug delivery strategies, including focused ultrasound, implantable drug-delivery systems, and engineered nanoparticles, hold potential for enhancing the bioavailability and therapeutic efficacy of treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Medullary thyroid carcinoma (MTC) is a rare but aggressive form of thyroid cancer accounting for over 10% of deaths related to thyroid malignancies. MTC can be either hereditary or sporadic. Although it can be cured if it is detected early and completely removed, most patients with MTC are diagnosed when the cancer has already spread beyond the thyroid gland, making it difficult to treat. Managing MTC is complex, despite the availability of newer treatment options like targeted therapy, which works in less than 30% of cases and can lead to severe side effects in some patients. MTC behaves differently in each patient, making the selection of appropriate treatments challenging, even for multidisciplinary teams of experts. This article aims to describe the challenges faced during the diagnostic workup and management of MTC patients. It highlights how holomics, which is an integrated approach combining various biological data types, and artificial intelligence (AI) can assist in improving patient outcomes. By simultaneously analyzing and integrating findings from biochemical, radiological, and histological investigations, genetic studies, and other sources, along with the personal information of a patient, AI can enhance decision-making processes. This innovative approach has the potential to personalize and optimize treatment strategies, leading to better management and improved outcomes for patients with MTC. Background/Objective: Medullary thyroid carcinoma (MTC) is a rare yet aggressive form of thyroid cancer comprising a disproportionate share of thyroid cancer-related mortalities, despite its low prevalence. MTC differs from other differentiated thyroid malignancies due to its heterogeneous nature, presenting complexities in both hereditary and sporadic cases. Traditional management guidelines, which are designed primarily for papillary thyroid carcinoma (PTC), fall short in providing the individualized care required for patients with MTC. In recent years, the sheer volume of data generated from clinical evaluations, radiological imaging, pathological assessments, genetic mutations, and immunological profiles has made it humanly impossible for clinicians to simultaneously analyze and integrate these diverse data streams effectively. This data deluge necessitates the adoption of advanced technologies to assist in decision-making processes. Holomics, which is an integrated approach that combines various omics technologies, along with artificial intelligence (AI), emerges as a powerful solution to address these challenges. Methods: This article reviews how AI-driven precision oncology can enhance the diagnostic workup, staging, risk stratification, management, and follow-up care of patients with MTC by processing vast amounts of complex data quickly and accurately. Articles published in English language and indexed in Pubmed were searched. Results: AI algorithms can identify patterns and correlations that may not be apparent to human clinicians, thereby improving the precision of personalized treatment plans. Moreover, the implementation of AI in the management of MTC enables the collation and synthesis of clinical experiences from across the globe, facilitating a more comprehensive understanding of the disease and its treatment outcomes. Conclusions: The integration of holomics and AI in the management of patients with MTC represents a significant advancement in precision oncology. This innovative approach not only addresses the complexities of a rare and aggressive disease but also paves the way for global collaboration and equitable healthcare solutions, ultimately transforming the landscape of treatment and care of patients with MTC. By leveraging AI and holomics, we can strive toward making personalized healthcare accessible to every individual, regardless of their economic status, thereby improving overall survival rates and quality of life for MTC patients worldwide. This global approach aligns with the United Nations Sustainable Development Goal 3, which aims to ensure healthy lives and promote well-being at all ages. [ABSTRACT FROM AUTHOR]

Background/Objectives: The integration of AI into dentistry holds promise for improving diagnostic workflows, particularly in the detection of dental pathologies and pre-radiotherapy screening for head and neck cancer patients. This study aimed to develop and validate an AI model for detecting various dental conditions, with a focus on identifying teeth at risk prior to radiotherapy. Methods: A YOLOv8 model was trained on a dataset of 1628 annotated panoramic radiographs and externally validated on 180 radiographs from multiple centers. The model was designed to detect a variety of dental conditions, including periapical lesions, impacted teeth, root fragments, prosthetic restorations, and orthodontic devices. Results: The model showed strong performance in detecting implants, endodontic treatments, and surgical devices, with precision and recall values exceeding 0.8 for several conditions. However, performance declined during external validation, highlighting the need for improvements in generalizability. Conclusions: YOLOv8 demonstrated robust detection capabilities for several dental conditions, especially in training data. However, further refinement is needed to enhance generalizability in external datasets and improve performance for conditions like periapical lesions and bone loss. [ABSTRACT FROM AUTHOR]

The rapidly evolving field of radiomics has shown that radiomic features are able to capture characteristics of both tumor and normal tissue that can be used to make accurate and clinically relevant predictions. In the present study we sought to determine if radiomic features can characterize the adverse effects caused by normal tissue injury as well as identify if human embryonic stem cell (hESC) derived extracellular vesicle (EV) treatment can resolve certain adverse complications. A cohort of 72 mice (n = 12 per treatment group) were exposed to X-ray radiation to the whole lung (3 × 8 Gy) or to the apex of the right lung (3 × 12 Gy), immediately followed by retro-orbital injection of EVs. Cone-Beam Computed Tomography images were acquired before and 2 weeks after treatment. In total, 851 radiomic features were extracted from the whole lungs and < 20 features were selected to train and validate a series of random forest classification models trained to predict radiation status, EV status and treatment group. It was found that all three classification models achieved significantly high prediction accuracies on a validation subset of the dataset (AUCs of 0.91, 0.86 and 0.80 respectively). In the locally irradiated lung, a significant difference between irradiated and unirradiated groups as well as an EV sparing effect were observed in several radiomic features that were not seen in the unirradiated lung (including wavelet-LLH Kurtosis, wavelet HLL Large Area High Gray Level Emphasis, and Gray Level Non-Uniformity). Additionally, a radiation difference was not observed in a secondary comparison cohort, but there was no impact of imaging machine parameters on the radiomic signature of unirradiated mice. Our data demonstrate that radiomics has the potential to identify radiation-induced lung injury and could be applied to predict therapeutic efficacy at early timepoints. [ABSTRACT FROM AUTHOR]

Introduction: Randomised evidence supports the use of partial breast irradiation (PBI) with targeted intraoperative radiotherapy (TARGIT-IORT) for early stage breast cancer, but prospective data from real-world adoption of this technique is also important. The aim of this study was to determine if the outcome reported in TARGIT-A trial could be replicated in large cohort of early stage breast cancer treated with TARGIT-IORT. Methods: This prospective observational study analysed all patients treated with TARGIT-IORT between 2004 and 2021 in a single national cancer institute. TARGIT-IORT during lumpectomy was performed according to the riskadapted TARGIT-A protocol using the Intrabeam® device. We analysed the completeness of follow up, 5-year in-breast-tumour-recurrence (IBTR), long term local recurrence free survival, distant disease-free survival, overall survival and breast-cancer-related survival, using the Kaplan-Meier method. A covariate analysis was performed to investigate risk factors for IBTR. We also analysed high grade toxicity events. Results: The study included 814 patients and the a median follow up was 72 months. The majority of patients (60.3%) received TARGIT-IORT as PBI modality ("exclusive IORT" group); 39.7% received additional EBRT. There was no significant difference between the 5 years IBTR for the whole study population and the "exclusive IORT" cohort (1.6% (95%CI=1.1-2.1%) and 2.5% (95%CI=1.7%- 3.3%) respectively). 5 years overall survival and tumour related survival were >95%. In 21% of patients with recurrence, breast was preserved. Radiotherapy toxicity (CTCAE Grade>2) was very rare (0.9%). Conclusions: This large single institute study found that breast cancer control and survival outcomes with TARGIT-IORT were consistent with TARGIT-A trial results. This "real world" experience confirmed that the randomised evidence showing the value of TARGIT-IORT as partial breast irradiation modality that can be replicated in routine clinical practice. [ABSTRACT FROM AUTHOR]

Alpha-lipoic acid (ALA) is a bioactive molecule with significant health effects. The biological action of ALA has been ascribed to the characteristic antioxidant properties of the oxidized form (ALA) and its reduced counterpart the dihydrolipoic acid (DHLA) system. The ALA/DHLA combination represents an ideal antioxidant since it can quench radicals, is able to chelate metals, is amphiphilic, and has no major adverse effects. This unique system is able to scavenge reactive oxygen species, exerting a major effect on tissue levels of reduced forms of other antioxidants, including glutathione. For this reason, ALA is also known as the "antioxidant of antioxidants". This review analyzes the antioxidant, anti-inflammatory, and neuroprotective effects of ALA and discusses its applications as an ameliorative tool for chronic diseases and those associated with oxidative stress. Results from in vitro and in vivo studies demonstrated that ALA modulates various oxidative stress pathways suggesting its application, alone or in combination with other functional substances, as a useful support in numerous conditions, in which the balance oxidant–antioxidant is disrupted, such as neurodegenerative disorders. Based on several successful clinical studies, it has been also established that oral ALA supplements are clinically useful in relieving the complications of diabetes and other disorders including cardiovascular diseases and nerve discomforts suggesting that ALA can be considered a useful approach to improving our health. [ABSTRACT FROM AUTHOR]