Search Results (61)

Eikenella corrodens is a facultative anaerobic Gram-negative bacillus, part of the normal oropharyngeal flora, with opportunistic pathogenic potential particularly in immunocompromised hosts. The progression from localized intracranial infections such as cerebritis and subdural empyema to secondary bloodstream infection represents a rare but clinically significant pathway, especially in immuno-compromised patients. Here, we report a case of secondary E. corrodens bacteremia following left temporal cerebritis and ipsilateral subdural empyema in a 50-year-old man with advanced nasopharyngeal carcinoma treated with nivolumab. The patient presented neurological deficits and systemic inflammatory response, suggesting for a bacterial infection. Neuroimaging confirmed the intracranial infectious foci and blood cultures identified E. corrodens via MALDI-TOF MS and 16S rRNA gene sequencing. We discuss how cancer-associated immune dysregulation and immune checkpoint inhibition could modulate host susceptibility and clinical presentation of infection, potentially facilitating microbial dissemination across compromised blood–brain barriers. Additionally, we examine the cases of E. corrodens bacteremia secondary to CNS and head and neck infections. This case underscores the importance of heightened clinical vigilance for secondary bacteremia in oncologic patients with CNS infections and highlights the need for integrated microbiological and radiological assessment to optimize outcomes. Full article

Background and objective: In Boron Neutron Capture Therapy, treatment planning is based on a weighted dose in which dose components are weighted with different biological effectiveness (RBE) factors. The most important one for the tumor dose is the compound dependent biological effectiveness (CBE) factor which weighs the boron dose. This was established for brain tumors from radiobiological experiments and has been extrapolated to the more recent application of BNCT to head and neck cancers. The purpose of this work is to study the validity of this assumption. Methods: Two cell lines, CAL-33 (head and neck squamous cell carcinoma) and A172 (Glioblastoma Multiforme), were irradiated with a very pure thermal-equivalent neutron beam after BPA incubation, and the surviving fraction of cells after irradiation was determined by clonogenicity assays. Results: The Compound Biological Effectiveness of both cell lines is similar, although for head and neck carcinoma, 10% higher values are systematically found. In addition to this, radiobiological coefficients for the different dose components (photon, neutron and boron) of BNCT in both cell lines are provided. Full article

Perfusion assessment is critical in clinical oncology, particularly in tumor characterization, intraoperative decision making, and postoperative outcome predictions. Hyperspectral imaging (HSI) has emerged as a promising, non-contact, non-invasive, and contrast-free modality capable of capturing spatial and spectral information related to tissue oxygenation and hemoglobin distribution. This study provides an up-to-date review of recent advances in the use of HSI for perfusion monitoring in clinical oncological applications, with a special focus on its adoption in laparoscopic surgeries, brain tumor delineation, and head and neck cancer interventions. The integration of HSI into surgical workflows and its potential to reduce complications are discussed. Overall, while HSI is emerging as an appealing, real-time, quantitative perfusion imaging modality, a lack of standardized protocols and interpretation guidelines pose the most significant challenges. Addressing these gaps through multicenter clinical trials is essential for advancing the routine use of HSI in oncological surgery. Full article

Near-infrared photoimmunotherapy (NIR-PIT) is a promising cancer treatment that uses near-infrared light to activate a conjugate of a monoclonal antibody (mAb) and a photoactivatable silica phthalocyanine dye (IRDye700DX: IR700). Unlike conventional photodynamic therapy (PDT), NIR-PIT selectively destroys targeted tumor cells while preserving the surrounding normal tissue and providing superior tissue penetration. Recently, NIR-PIT has been approved for the treatment of unresectable recurrent head and neck cancers in Japan. It induces highly selective cancer cell death; therefore, it is expected to be a new curative treatment option for various cancers, including brain tumors. In this review, we compare the principles of NIR-PIT and PDT and discuss the potential applications of NIR-PIT for brain tumors. We selected targetable proteins across various types of brain tumors and devised a strategy to effectively pass the mAb–IR700 conjugate through the blood–brain barrier (BBB), which is a significant challenge for NIR-PIT in treating brain tumors. Innovative approaches for delivering the mAb–IR700 conjugate across the BBB include exosomes, nanoparticle-based systems, and cell-penetrating peptides. Small-molecule compounds, such as affibodies, are anticipated to rapidly accumulate in tumors within intracranial models, and our preliminary experiments demonstrated rapid uptake. NIR-PIT also induces immunogenic cell death and activates the anti-tumor immune response. Overall, NIR-PIT is a promising approach for treating brain tumors. It has the potential to overcome the limitations of conventional therapies and offers new hope to patients with brain tumors. Full article

Background: Health-related quality of life (HRQoL) is an important patient-reported outcome for all cancer patients, including adult patients with rare solid cancers. However, current knowledge of HRQoL in this population is limited, which hinders the delivery of personalized care. This review aimed to explore the heterogeneity of HRQoL among adult patients with a solid rare cancer across the ten European Reference Network for Rare Adult Solid Cancers (EURACAN) domains and to summarize the HRQoL measures used in clinical research. Methods: A systematic literature search was conducted to identify all clinical studies assessing HRQoL in adult patients with a solid rare cancer. Four databases (MEDLINE, PubMed, PsycINFO, and Web of Science/Scopus) were searched (February 2023). Results: The search yielded 18,704 articles, of which 1416 articles were fully screened and 463 were eligible for analysis. Of these, 397 studies used generic tools to assess HRQoL, while 270 used tumor-specific instruments. Three EURACAN domains (sarcoma, endocrine tumors, and thoracic tumors) primarily assessed HRQoL using generic questionnaires. Additionally, the rare gynecological tumor, rare male genitourinary, and sarcoma EURACAN domains lacked specific HRQoL measures. Brain, head and neck, and uveal melanoma EURACAN domains used tumor- or domain-specific questionnaires in more than half of the studies. Conclusions: This state-of-the-art literature review shows that HRQoL assessment is gradually becoming more prevalent in adult solid rare cancer research. A combination of generic, tumor-specific, and domain-specific questionnaires across various rare cancer domains has proven effective in capturing a broad range of HRQoL issues. However, many EURACAN domains still lack specific strategies for assessing HRQoL, which limits the ability to fully understand and address patients’ experiences. Future research should prioritize developing comprehensive and robust HRQoL measurement strategies and tools to enable meaningful clinical research and to ensure that the patient voice is incorporated in their clinical care. Full article

Late-onset Alzheimer’s disease (LOAD) is a chronic, multifactorial, and progressive neurodegenerative disease that associates with aging and is highly prevalent in our older population (≥65 years of age). This hypothesis generating this narrative review will examine the important role for the use of sodium thiosulfate (STS) as a possible multi-targeting treatment option for LOAD. Sulfur is widely available in our environment and is responsible for forming organosulfur compounds that are known to be associated with a wide range of biological activities in the brain. STS is known to have (i) antioxidant and (ii) anti-inflammatory properties; (iii) chelation properties for calcium and the pro-oxidative cation metals such as iron and copper; (iv) donor properties for hydrogen sulfide production; (v) possible restorative properties for brain endothelial-cell-derived bioavailable nitric oxide. Thus, it becomes apparent that STS has the potential for neuroprotection and neuromodulation and may allow for an attenuation of the progressive nature of neurodegeneration and impaired cognition in LOAD. STS has been successfully used to prevent cisplatin oxidative-stress-induced ototoxicity in the treatment of head and neck and solid cancers, cyanide and arsenic poisoning, and fungal skin diseases. Most recently, intravenous STS has become part of the treatment plan for calciphylaxis globally due to vascular calcification and ischemia-induced skin necrosis and ulceration. Side effects have been minimal with reports of metabolic acidosis and increased anion gap; as with any drug treatment, there is also the possibility of allergic reactions, possible long-term osteoporosis from animal studies to date, and minor side-effects of nausea, headache, and rhinorrhea if infused too rapidly. While STS poorly penetrates the intact blood–brain barrier(s) (BBBs), it could readily penetrate BBBs that are dysfunctional and disrupted to deliver its neuroprotective and neuromodulating effects in addition to its ability to penetrate the blood–cerebrospinal fluid barrier of the choroid plexus. Novel strategies such as the future use of nano-technology may be helpful in allowing an increased entry of STS into the brain. Full article

Background: Firstly, 5-hydroxytryptamine G-protein-coupled receptors (HTGPCRs) are a family of 13 genes associated with cancer progression. Nevertheless, a comprehensive understanding of HTGPCRs in cancer remains largely lacking. Method: We tested the gene expression levels and prognostic values for the HTGPCRs in relation to pan-cancer. A subsequent analysis examined the relationships among HTGPCR expression and clinical characteristics, immune subtypes, stemness scores, tumor microenvironments (TMEs), single-cell analyses, and drug sensitivity. Result: A significant difference in HTGPCR expression was found between normal tissues and tumors. HTR1D/2C expressed higher levels in breast invasive carcinoma (BRCA), colon adenocarcinoma, and liver hepatocellular carcinoma. HTGPCR gene expression was correlated with prognosis in many cancers. HTR1D/2C were associated with poorer overall survival for head and neck squamous cell carcinoma. In addition, HTGPCR expression correlated significantly with the stemness scores of RNA and DNA, TMB, and MSI, as well as stromal and immune scores of pan-cancer patients. Additionally, the expression of HTR2A/2B/7 was correlated significantly with immune cells and immune checkpoint genes in a variety of cancers, such as BRCA, brain lower-grade glioma, and lung adenocarcinoma. Immune regulation and TME were both regulated by HTGPCRs. Using single-cell analysis, we found that the gene set of HTGPCRs correlated with many cancer-related functional states in retinoblastoma. Moreover, drug sensitivity and HTR4 were significantly correlated. Furthermore, we validated results in breast cancer and found knockdown of HTR1D inhibited breast cancer cell growth and metastasis. Conclusion: As prognostic indicators, HTGPCRs hold considerable promise and offer insights into the therapeutic targets for malignancy. Full article

The topic of quantitative imaging in radiation therapy was presented as a “Masterclass” at the 2023 annual meeting of the American Society of Radiation Oncology (ASTRO). Dual-energy computed tomography (CT) and single-positron computed tomography were reviewed in detail as the first portion of the meeting session, with data showing utility in many aspects of radiation oncology including treatment planning and dose response. Positron emission tomography/CT scans evaluating the functional volume of lung tissue so as to provide optimal avoidance of healthy lungs were presented second. Advanced brain imaging was then discussed in the context of different forms of magnetic resonance scanning methods as the third area noted with significant discussion of ongoing research programs. Quantitative image analysis was presented to provide clinical utility for the analysis of patients with head and neck cancer. Finally, quality assurance was reviewed for different forms of quantitative imaging given the critical nature of imaging when numerical valuation, not just relative contrast, plays a crucial role in clinical process and decision-making. Conclusions and thoughts are shared in the conclusion, noting strong data supporting the use of quantitative imaging in radiation therapy going forward and that more studies are needed to move the field forward. Full article

Proton therapy is increasingly widespread and requires an accelerator to provide the high energy protons. Most often, the accelerators used for proton therapy are cyclotrons and the maximum initial beam energy (MIBE) is about 230 MeV or more to be able to achieve a range of approximately 30 cm in water. We ask whether such a high energy is necessary for adequate dosimetry for pathologies to be treated with proton beams. Eight patients of different clinical sites (brain, prostate, and head and neck cancers) were selected to conduct this study. We analyzed the tumor dose coverage and homogeneity, as well as healthy tissue protection for MIBE values of 120, 160, 180, 200 and 230 MeV. For each patient, a proton plan was developed using the particular MIBE and then using multifield optimization (MFO). In this way, 34 plans in total were generated to fulfill the unique clinical goals. This study found that MIBE of 120 MeV for brain tumors; 160 MeV for head and neck cancer; and remarkably, for prostate cancer, only 160 MeV for one patient case and 180 MeV for the remainder satisfied the clinical goals (words: 187 < approx. 200 words or less) Full article

Objective: This study aims to examine whether radiation therapy doses are related to incidences of carotid artery stenosis and brain necrosis in a large-scale real-world database. Methods: We identified a cohort of HNC patients from the catastrophic illness patient dataset using ICD-9 or ICD-10 to compare the incidence and risks of carotid artery stenosis (CAS) and brain necrosis (RIBN) in patients who received a radiation therapy dose of ≥5400 cGy/30 fractions (group A) with those who received a radiation therapy dose of <5400 cGy/30 fractions (group B). The incidence and hazard ratios were quantified using Cox proportional hazards models. Results: A total of 19,964 patients were identified in group A and group B. Among them, 965 and 863 cases of CAS and 435 and 359 cases of RIBN were identified in group A and group B, respectively. There was no statistically significant association between the two groups for CAS risk, whereas there was a statistically significant association between the two groups for RIBN risk. The most common primary site of head and neck cancers was the nasopharynx (1144 of 19,964, 5.73%). Conclusions: Our study suggests that RT may increase the risk of carotid stenosis and brain necrosis in patients with NPC. To ensure patient safety during treatment, the optimal balance between tumor control and toxicity prevention in individual patients through minimization of the radiation dose to all relevant OARs must be properly understood. Full article

Introduction: The main goal of radiotherapy (RT) is to deliver a precise dose to the target while sparing the surrounding normal tissue and minimizing side effects. Appropriate patient immobilization is crucial, especially for head and neck cancer (HNC) and Brain Cancer (BC). Conventional closed-face masks (CFMs), while effective in minimizing head motion, can cause significant discomfort, anxiety, and claustrophobia. Open-face masks (OFMs) have been developed to increase patient comfort while providing precise immobilization. Methods: Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) extension for scoping reviews and the Arskey and O’Malley framework, an electronic search of EMBASE, PubMed, SCOPUS, and Web of Science was conducted to identify original studies reporting the use and description of OFMs in clinical practice up to April 2024. The inclusion criteria were English-language articles focusing on OFMs for HNC and BC patients undergoing RT. Results: Of 618 titles, 19 articles fulfilled the selection criteria. Most studies were comparative (n = 13) or observational (n = 6). The articles were categorized by treatment site, resulting in three groups: BC (n = 14, 68.4%), HNC (n = 4, 21.4%), and mixed (n = 2, 10.5%), which includes both BC and HNC. Of note, 82.4% (n = 16) of the included studies were published from 2020 onwards, emphasizing the recent adoption of OFM in clinical practice. Conclusions: The reviewed studies show that OFMs, in combination with SGRT, offer significant advantages in terms of patient comfort and positioning accuracy in HNC and BC treatments. Reproducibility in the sub-millimeter and sub-degree range can be achieved, which supports the use of OFMs in clinical practice. Future research should explore innovative combinations of immobilization and monitoring to further improve RT outcomes and ensure precise treatment while increasing patient comfort. Full article

Background. The diagnosis and treatment of head and neck tumors present significant challenges due to their infiltrative nature and diagnostic hindrances such as the blood–brain barrier. The intricate anatomy of the head and neck region also complicates the clear identification of tumor boundaries and assessment of tumor characteristics. Aim. This review aims to explore the efficacy of molecular imaging techniques that employ targeted contrast agents in head and neck cancer imaging. Head and neck cancer imaging benefits significantly from the combined advantages of CT and MRI. CT excels in providing swift, high-contrast images, enabling the accurate localization of tumors, while MRI offers superior soft tissue resolution, contributing to the detailed evaluation of tumor morphology in this region of the body. Many of these novel contrast agents have integration of dual-modal, triple-modal, or even dual-tissue targeting imaging, which have expanded the horizons of molecular imaging. Emerging contrast agents for the purpose of MRI and CT also include the widely used standards in imaging such as gadolinium and iodine-based agents, respectively, but with peptide, polypeptide, or polymeric functionalizations. Relevance for patients. For patients, the development and use of these targeted contrast agents have potentially significant implications. They benefit from the enhanced accuracy of tumor detection and characterization, which are critical for effective treatment planning. Additionally, these agents offer improved imaging contrast with the added benefit of reduced toxicity and bioaccumulation. The summarization of preclinical nanoparticle research in this review serves as a valuable resource for scientists and students working towards advancing tumor diagnosis and treatment with targeted contrast agents. Full article

Cancer disclosure represents a complex healthcare dynamic. Physicians or caregivers may be prompted to withhold diagnosis information from patients. This study aims to comprehensively map and synthesize available evidence about diagnosis nondisclosure regarding head and neck cancer (HNC) patients. Following the Joanna Briggs Institute guidelines, a scoping review was conducted across major databases without period restriction, yielding 9238 publications. After screening and selection, a descriptive synthesis was conducted. Sixteen studies were included, primarily conducted in academic settings (75%) from Europe and Asia, with a total population of 662 patients predominantly diagnosed with brain, oral, pharyngeal, or laryngeal tumors. Remarkably, 22.51% of patients were unaware of their diagnosis. Although physicians were the main source of diagnostic information (35%), they reported to often use vague terms to convey malignancy. Additionally, 13.29% of patients were aware of their diagnosis from sources other than doctors or caregivers. Caregivers (55%) supported diagnosis concealment, and physicians tended to respect family wishes. A high diagnosis-to-death interval, education, and age significantly influenced diagnosis disclosure. HNC patients expressed a desire for personalized open communication. Multiple factors influenced the decision on diagnosis disclosure. Current evidence on this topic varies significantly, and there is limited research on the consequences of nondisclosure. These findings reflect the underestimation of the patients’ outlook in the diagnosis process and highlight the need for further research, aiming to establish open communication and patient autonomy during the oncological journey. Full article

Background: In current clinical practice, intensity-modulated proton therapy (IMPT) head and neck cancer (HNC) plans are generated using a constant relative biological effectiveness (cRBE) of 1.1. The primary goal of this study was to explore the dosimetric impact of proton range uncertainties on RBE-weighted dose (RWD) distributions using a variable RBE (vRBE) model in the context of bilateral HNC IMPT plans. Methods: The current study included the computed tomography (CT) datasets of ten bilateral HNC patients who had undergone photon therapy. Each patient’s plan was generated using three IMPT beams to deliver doses to the CTV_High and CTV_Low for doses of 70 Gy(RBE) and 54 Gy(RBE), respectively, in 35 fractions through a simultaneous integrated boost (SIB) technique. Each nominal plan calculated with a cRBE of 1.1 was subjected to the range uncertainties of ±3%. The McNamara vRBE model was used for RWD calculations. For each patient, the differences in dosimetric metrices between the RWD and nominal dose distributions were compared. Results: The constrictor muscles, oral cavity, parotids, larynx, thyroid, and esophagus showed average differences in mean dose (D_mean) values up to 6.91 Gy(RBE), indicating the impact of proton range uncertainties on RWD distributions. Similarly, the brachial plexus, brain, brainstem, spinal cord, and mandible showed varying degrees of the average differences in maximum dose (D_max) values (2.78–10.75 Gy(RBE)). The D_mean and D_max to the CTV from RWD distributions were within ±2% of the dosimetric results in nominal plans. Conclusion: The consistent trend of higher mean and maximum doses to the OARs with the McNamara vRBE model compared to cRBE model highlighted the need for consideration of proton range uncertainties while evaluating OAR doses in bilateral HNC IMPT plans. Full article

The quality of radiation therapy (RT) treatment plans directly affects the outcomes of clinical trials. KBP solutions have been utilized in RT plan quality assurance (QA). In this study, we evaluated the quality of RT plans for brain and head/neck cancers enrolled in multi-institutional clinical trials utilizing a KBP approach. The evaluation was conducted on 203 glioblastoma (GBM) patients enrolled in NRG-BN001 and 70 nasopharyngeal carcinoma (NPC) patients enrolled in NRG-HN001. For each trial, fifty high-quality photon plans were utilized to build a KBP photon model. A KBP proton model was generated using intensity-modulated proton therapy (IMPT) plans generated on 50 patients originally treated with photon RT. These models were then applied to generate KBP plans for the remaining patients, which were compared against the submitted plans for quality evaluation, including in terms of protocol compliance, target coverage, and organ-at-risk (OAR) doses. RT plans generated by the KBP models were demonstrated to have superior quality compared to the submitted plans. KBP IMPT plans can decrease the variation of proton plan quality and could possibly be used as a tool for developing improved plans in the future. Additionally, the KBP tool proved to be an effective instrument for RT plan QA in multi-center clinical trials. Full article