Effectiveness of Comprehensive Intervention Programme on Quality of life, fatigue, self-efficacy, and psychosocial distress among head and neck cancer patients receiving radiotherapy.

PURPOSE: The study aimed at evaluating the Effectiveness of Comprehensive Intervention Programme (CIP) on Quality of life (QOL), fatigue, self-efficacy, and psychosocial distress among Head and Neck Cancer (HNC) patients receiving radiotherapy treatment. METHODS: Single-centre non-RCT time series study was conducted among 134 HNC patients (67 observed, followed by 67 subjected to CIP). FACT- H&N, FACT-F, Cancer Behavior Inventory and psychosocial distress scales were used to assess QOL, fatigue, self-efficacy, and psychosocial distress respectively. CIP was provided to the intervention arm twice a week during the course of radiation therapy along with the standard care; the control arm received only standard care. Data were collected before commencing radiotherapy, and post-test assessments were carried out at the end of radiotherapy treatment, and at 3 and 6 months after completion of radiotherapy. RESULTS: Repeated measures ANOVA revealed a statistically significant improvement with CIP in QOL (F (1.917) = 454.103, p = 0.001), fatigue (F (2.106) = 183.775, p = 0.001), self-efficacy (F (2.429) = 190.861, p = 0.001), and psychosocial distress (F (2.288) = 290.105, p = 0.001) in the intervention arm. CONCLUSION: The CIP implemented to address multitude of issues in HNC patients receiving radiotherapy, proved to be effective in reducing the impact of treatment on QOL, fatigue, self-efficacy and psychosocial distress in HNC patients receiving radiotherapy.

Comparison of Submental Surface Electromyography during Dry Swallow between Irradiated Head and Neck Cancer Survivors and Normal Individuals.

INTRODUCTION: This study compared the submental surface electromyography (sEMG) duration and amplitude during dry swallowing between irradiated head and neck cancer (HNC) survivors and age-matched normal individuals. Further, the relationship between submental and infrahyoid sEMG in the irradiated HNC group was explored. METHOD: Forty participants (20 HNC survivors and 20 age-matched normal individuals) participated in this study. The HNC survivors had completed organ preservation cancer treatment (at least 1-month post-treatment). They were on a complete oral diet without enteral supplementation (FOIS score> 4). Submental and infrahyoid sEMG activity was calculated for three trials of saliva swallow for each participant using sEMG. The duration and amplitude parameters considered were: onset duration - duration from the onset of swallowing to the maximum amplitude, offset duration - duration from the maximum amplitude to the end of the swallowing activity, total duration, and maximum amplitude. RESULTS: The study found that irradiated HNC survivors exhibited prolonged temporal measures, particularly in the offset duration, which suggested a delayed descent of the hyolaryngeal complex during swallowing. Additionally, the HNC group showed a positive correlation between submental and infrahyoid sEMG. Furthermore, it was observed that the rate of increase in the duration of submental sEMG during subsequent swallowing was greater in HNC survivors which could be due to reduced salivation. CONCLUSION: Compared to age-matched normal individuals, irradiated HNC survivors manifest alterations in the submental muscle activities during dry swallowing as measured using sEMG. The temporal and amplitude changes are likely to have arisen as a consequence of postradiation changes.

Interventions to improve quality of life in patients with head and neck cancers receiving radiation therapy: a scoping review.

BACKGROUND: Quality of life (QOL) is impaired in patients with head and neck cancers (HNC) due to illness and treatment-associated morbidity. Although there is evidence from the studies on interventions' role in improving QOL receiving radiation therapy, these are not systematically synthesised. In this scoping review, we searched and synthesised the evidence on interventions to improve the QOL and its impact among patients with HNCs. METHODS: This scoping review was conducted using the framework proposed by Arksey and O'Malley, and the extensions suggested by Levac et al. were incorporated. Two reviewers independently searched four electronic databases using key thesaurus and free-text terms, and the data was extracted, tabulated, synthesised and reported as categories. RESULTS: Seventy-nine papers reported various interventions of diverse nature such as pharmacological, physical, nutritional, complementary and alternative therapies, psychosocial, oral care related, laser and photobiomodulation therapies, rehabilitative, educational, technology-based, surgical, device-related and nurse lead interventions. Most studies reported clinically meaningful impact of interventions on QOL, although the outcome differences were often statistically insignificant. Few studies reported a combination of interventions to address the multidimensional concerns faced by patients with HNCs. None of the studies examined the impact of interventions on QOL among long-term survivors of HNCs. CONCLUSION: As QOL concerns in patients with HNCs are multifaceted, more extensive studies with complex multi-component interventions and robust research designs are warranted.

Attributes of Psychosocial Distress from the Perspectives of Head-and-Neck Cancer Patients - A Thematic Analysis.

Objectives: Patients diagnosed with head-and-neck cancer (HNC) face unique challenges in comparison to other types of cancers. Sources of psychosocial distress (PSD) are multifactorial and recognising the key attributes would facilitate better understanding of the experienced distress, potentially enabling directed intervention strategies. The present research was conducted to explore the key attributes of PSD from HNC patients' perspective to develop a tool. Material and Methods: The study adopted a qualitative approach. The data were collected from nine HNC patients receiving radiotherapy through focus group discussion. Data were transcribed, read and reread through for searching the meanings and patterns, to familiarise with the data and obtain ideas on experiences related to PSD. Similar experiences identified across the dataset were sorted and then collated into themes. Detailed analysis of themes and related quotes of the participants are reported with each theme. Results: The codes generated from the study are grouped under four major themes; 'Irksome symptoms are distressing,' 'Distressing physical disability inflicted by the situation,' 'Social Curiosity - a distressing element' and 'Distressing uncertainty of future'. The attributes of PSD and the magnitude of psychosocial problems were reflected in the findings. Conclusion: Psychosocial health of HNC patients is greatly impacted due to disease and/or treatment. Dynamic patterns of attributes identified from the study contributed to developing a tool on PSD. The findings of this study also necessitate the need for constructing an intervention for reducing PSD based on the attributes from the HNC patient's perspective.

Health literacy in communication, decision-making and outcomes among cancer patients, their families and clinicians in India: A multicentre cross-sectional qualitative study.

OBJECTIVE: Cancer patients in India prefer full information regarding diagnosis and prognosis, but evidence suggests poor insight. This study aimed to identify the role of health literacy among adult patients living with cancer, their families and health professionals in decision-making and treatment outcomes in India. METHODS: This cross-sectional in-depth study recruited patients, families and clinicians from three centers. Inductive thematic analysis informed a novel conceptual model. RESULTS: We recruited n = 34 cancer patients, n = 33 family members, n = 11 doctors and n = 14 nurses (N = 92). Principle emergent themes were the following: (1) Preferences and dynamics of diagnosis and prognosis disclosure, for example, the dominant preference was for families who held hope for cure to discourage disclosure; clinicians sometimes disclosed in line with perceived ability to pay for treatment. (2) Understanding of disease and its treatment options (etiology, potential trajectory, treatment options), for example, lay understandings of cancer etiology as contamination from outside the home, and reluctance of patients to ask questions of clinicians. (3) Priorities in decision-making, for example, not engaging patients due to fear of patient distress, patients initiated on anticancer treatments without knowledge or consent, pursuing futile treatments. (4) Anxieties over finances and outcomes (disclosure, decision-making, care pathways), for example, clinicians attempting to reduce families pursuing expensive and inappropriate treatment options with patients who have poor insight, catastrophic spending based on poor decisions. CONCLUSION: The novel evidence-based health literacy model offers potential for feasible and acceptable intervention to support families in communication, disclosure and decision-making. This may improve patients' access to informed, appropriate care pathways.

Impact of COVID-19 on cancer care in India: a cohort study.

BACKGROUND: The COVID-19 pandemic has disrupted health-care systems, leading to concerns about its subsequent impact on non-COVID disease conditions. The diagnosis and management of cancer is time sensitive and is likely to be substantially affected by these disruptions. We aimed to assess the impact of the COVID-19 pandemic on cancer care in India. METHODS: We did an ambidirectional cohort study at 41 cancer centres across India that were members of the National Cancer Grid of India to compare provision of oncology services between March 1 and May 31, 2020, with the same time period in 2019. We collected data on new patient registrations, number of patients visiting outpatient clinics, hospital admissions, day care admissions for chemotherapy, minor and major surgeries, patients accessing radiotherapy, diagnostic tests done (pathology reports, CT scans, MRI scans), and palliative care referrals. We also obtained estimates from participating centres on cancer screening, research, and educational activities (teaching of postgraduate students and trainees). We calculated proportional reductions in the provision of oncology services in 2020, compared with 2019. FINDINGS: Between March 1 and May 31, 2020, the number of new patients registered decreased from 112 270 to 51 760 (54% reduction), patients who had follow-up visits decreased from 634 745 to 340 984 (46% reduction), hospital admissions decreased from 88 801 to 56 885 (36% reduction), outpatient chemotherapy decreased from 173634 to 109 107 (37% reduction), the number of major surgeries decreased from 17 120 to 8677 (49% reduction), minor surgeries from 18 004 to 8630 (52% reduction), patients accessing radiotherapy from 51 142 to 39 365 (23% reduction), pathological diagnostic tests from 398 373 to 246 616 (38% reduction), number of radiological diagnostic tests from 93 449 to 53 560 (43% reduction), and palliative care referrals from 19 474 to 13 890 (29% reduction). These reductions were even more marked between April and May, 2020. Cancer screening was stopped completely or was functioning at less than 25% of usual capacity at more than 70% of centres during these months. Reductions in the provision of oncology services were higher for centres in tier 1 cities (larger cities) than tier 2 and 3 cities (smaller cities). INTERPRETATION: The COVID-19 pandemic has had considerable impact on the delivery of oncology services in India. The long-term impact of cessation of cancer screening and delayed hospital visits on cancer stage migration and outcomes are likely to be substantial. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

ZNF471 modulates EMT and functions as methylation regulated tumor suppressor with diagnostic and prognostic significance in cervical cancer.

Cervical cancer (CC) is a leading cause of cancer-related death among women in developing countries. However, the underlying mechanisms and molecular targets for therapy remain to be fully understood. We investigated the epigenetic regulation, biological functions, and clinical utility of zinc-finger protein 471 (ZNF471) in CC. Analysis of cervical tissues and five independent public datasets of CC showed significant hypermethylation of the ZNF471 gene promoter. In CC cell lines, promoter DNA methylation was inversely correlated with ZNF471 expression. The sensitivity and specificity of the ZNF471 hypermethylation for squamous intraepithelial lesion (SIL) vs tumor and normal vs tumor was above 85% with AUC of 0.937. High methylation and low ZNF471 expression predicted poor overall and recurrence-free survival. We identified -686 to +114 bp as ZNF471 promoter, regulated by methylation using transient transfection and luciferase assays. The promoter CpG site methylation of ZNF471 was significantly different among cancer types and tumor grades. Gal4-based heterologous luciferase reporter gene assays revealed that ZNF471 acts as a transcriptional repressor. The retroviral mediated overexpression of ZNF471 in SiHa and CaSki cells inhibited growth, proliferation, cell migration, invasion; delayed cell cycle progression in vitro by increasing cell doubling time; and reduced tumor growth in vivo in nude mice. ZNF471 overexpression inhibited key members of epithelial-mesenchymal transition (EMT), Wnt, and PI3K-AKT signaling pathways. ZNF471 inhibited EMT by directly targeting vimentin as analyzed by bioinformatic analysis, ChIP-PCR, and western blotting. Thus, ZNF471 CpG specific promoter methylation may determine the prognosis of CC and could function as a potential tumor suppressor by targeting EMT signaling.

Enumeration of deregulated miRNAs in liquid and tissue biopsies of cervical cancer.

OBJECTIVE: The altered miRNAs expression in cervical cancer tissue can be a critical player during tumorigenesis, may contribute to tumor cell heterogeneity and may determine distinct phenotypes within the tumor. Recent studies have highlighted the role of circulating miRNAs as a minimally-invasive biomarker and its potential as biosignature to complement routine tissue-based procedures. METHODS: In order to determine whether miRNAs in serum can indicate changes in cervical tissue specimens, we performed small RNA sequencing and selected miRNAs were validated using qRT-PCR in serum and tissue specimens (n = 115). Further, luciferase assay were performed to investigate the interactions between hsa-miR-409-3p and hsa-miR-454-3p binding sites on 3'UTR region of MTF2 and ST18 respectively. RESULTS: We have identified a total of 14 differentially expressed miRNAs common in serum and tissue specimens. Among them, hsa-miR-17-5p, hsa-miR-32-5p and hsa-miR-454-3p were upregulated while, hsa-miR-409-3p was downregulated in serum and tissue of cervical cancer subjects. Our in-silico small RNA sequencing data analysis identified isomiRs and classified miRNA into clusters and subtypes (exonic, intronic and intergenic) with respect to the expression status in serum and tissue specimens. Expression level of hsa-miR-409-3p and hsa-miR-454-3p were inversely correlated with their target genes MTF2 and ST18 levels respectively in human cervical cancer specimens. Luciferase assay demonstrated that hsa-miR-409-3p and hsa-miR-454-3p functionally interacts with 3'-UTR of MTF2 and ST18 respectively to decrease their activity. CONCLUSION: Our results support the significant role of circulating miRNAs in disease dissemination and their potential utility as biosignatures of clinical relevance.

Patterns of Recurrence, Long-term Survival and Toxicity Analysis of Endometrial Adenocarcinoma Patients Reclassified Under the Recent ESMO-ESGO-ESTRO Stratification: Seven-Year Results From a Single Institution.

AIM: The aim of this study was to report the patterns of recurrence, locoregional control, and survival of patients diagnosed with endometrial adenocarcinomas over a 7-year period after reclassifying them under the recent ESMO-ESGO-ESTRO (European Society of Medical Oncology/European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology) consensus classification. METHODS: Archives of a single institution from 2008 to 2014 were studied and patients with stages I-II endometrial adenocarcinoma were reclassified as per the new classification for uniformity. On magnetic resonance imaging, if found to be stage I, total abdominal hysterectomy with bilateral salpingo-oophorectomy alone was performed. The indications for adjuvant external beam radiotherapy (EBRT) and vaginal brachytherapy (VBT) were based on standard recommendations. Survival was calculated from Kaplan-Meier curves, and toxicity was recorded using Common Terminology Criteria for Adverse Events version 3. RESULTS: Of the 132 patients registered, 101 patients were included for analysis. A total of 18 patients have died, and information on outcome is available for 84% of patients. Five patients were metastatic at presentation. Five patients received definitive EBRT + intracavitary brachytherapy because of surgical inoperability, four of whom are disease-free locoregionally with median overall survival of 33.8 months. Of the 91 patients operated on, the incidence of low, intermediate, high-intermediate, and high risk was 34%, 29%, 2%, and 19%, whereas 16% were stage III. The overall recurrence rates were 10%, 15%, and 23% for low, intermediate, and high risk, respectively. With median follow-up of 32 months (range, 2-93 months), the disease-free survival for low, intermediate, and high risk and stage III were 92%, 81%, and 64% and 55%, whereas the mean survival for the same groups were 53, 44, and 34 and 22 months, respectively (P = 0.047). External beam radiotherapy resulted in significantly higher proctitis than VBT alone (P = 0.02). The median time to cystitis, proctitis, and enteritis were 27, 19, and 28 months, respectively. CONCLUSIONS: Recurrence rates, survival rates, and the patterns of recurrence are comparable with published literature and partly validates the ESMO-ESGO-ESTRO consensus statement. Addition of EBRT significantly increases risk of late proctitis as compared with VBT alone.

Speech-Language Pathologist's Pattern of Practice in the Rehabilitation of Head and Neck Cancer patients across Hospitals in India.

OBJECTIVE: India has a significant burden of Head and Neck cancer (HNC) patients. Patients afflicted with HNC often encounter difficulties in speech, voice, and swallowing, either due to the disease itself or the treatment they receive. The rehabilitation of HNC patients is crucial, and Speech and Language Pathologists (SLPs) have a significant role in it. The current study aimed to understand the practices followed by SLPs in India while rehabilitating HNC patients. METHODS: A questionnaire was developed and validated by five Speech-language pathologists, before circulation as an E-survey. The target participants were SLPs working in hospitals across India. The final online version of the questionnaire remained open for eight weeks. RESULT: A total of 75 Hospital-based SLPs working in India participated in the survey. The responses depict notable trends and differences in the assessment and management approaches. HNC patients who had undergone surgery were more likely to be referred for rehabilitation than those who received non-surgical treatments. Only 36% of the SLPs reported getting pre-operative referrals for HNC patients. The time point for initial assessment and intervention, as well as the protocols used, varied across different hospitals. About 50% of participants had instrumental swallow evaluation facilities in their hospitals, and the majority of hospitals only used instrumental swallow evaluation for 1-3 assessments per week. CONCLUSION: Variability exists in several aspects of SLP practice for HNC patients offered across Hospitals in India. All HNC patients do not get access to speech-language pathology services. Developing standardized protocols towards early evaluation, intervention and enhancing compliance could improve SLP-led rehabilitation of HNC patients in India.

Profiling of swallowing function in head and neck cancer patients prior to radiation therapy-Findings from a tertiary hospital in South India.

Purpose: Head and neck cancer (HNC) patients often face difficulties with swallowing, which can be due to the cancer itself or the treatment modalities like radiation therapy. The presentation of HNC can vary between developing and developed countries due to socioeconomic factors. The current study aimed to profile the swallowing function of HNC patients before starting radiation therapy in a tertiary hospital in India. Method: This cross-sectional observational study examined patients with HNC who were scheduled for radiation therapy. The Functional Oral Intake Scale (FOIS) and Karnofsky Performance Status Scale were used to assess the patients' swallowing status and functional abilities, respectively. The study also evaluated the relationship between swallowing function and clinical-demographic factors. Results: Our assessment of 162 HNC patients found that the cancer site significantly affects swallowing. Although 92% of patients had an oral diet, 64% made dietary modifications. Patients with non-oral intake had either oral or pharyngeal cancer, and over 80% of oral cancer patients and 60% of those with pharyngeal cancer had already made changes to their diet. Patients with laryngeal cancer had a better oral intake, with 58% reporting no swallowing issues. Conclusion: Patients with HNC scheduled for radiation therapy may experience varying degrees of swallowing difficulty. Early intervention and teaching of safe swallowing strategies are crucial to prepare for the potential worsening of swallowing difficulties resulting from the treatment. Advanced tumor stages and oral/pharyngeal cancers increase the risk of significant swallowing issues.

Low-dose exposure to malathion and radiation results in the dysregulation of multiple neuronal processes, inducing neurotoxicity and neurodegeneration in mouse.

Neurodegenerative disorders are a debilitating and persistent threat to the global elderly population, carrying grim outcomes. Their genesis is often multifactorial, with a history of prior exposure to xenobiotics such as pesticides, heavy metals, enviornmental pollutants, ionizing radiation etc,. A holistic molecular insight into their mechanistic induction upon single or combinatorial exposure to different toxicants is still unclear. In the present study, one-month-old C57BL/6 male mice were administered orally with malathion (50 mg/kg body wt. for 14 days) and single whole-body radiation (0.5 Gy) on the 8th day. Post-treatment, behavioural assays for exploratory behaviour, memory, and learning were performed. After sacrifice, brains were collected for histology, biochemical assays, and transcriptomic analysis. Transcriptomic analysis revealed several altered processes like synaptic transmission and plasticity, neuronal survival, proliferation, and death. Signalling pathways like MAPK, PI3K-Akt, Apelin, NF-κB, cAMP, Notch etc., and pathways related to neurodegenerative diseases were altered. Increased astrogliosis was observed in the radiation and coexposure groups, with significant neuronal cell death and a reduction in the expression of NeuN. Sholl analysis, dendritic arborization and spine density studies revealed decreased total apical neuronal path length and dendritic spine density. Reduced levels of the antioxidants GST and GSH and acetylcholinesterase enzyme activity were also detected. However, no changes were seen in exploratory behaviour or learning and memory post-treatment. Thus, explicating the molecular mechanisms behind malathion and radiation can provide novel insights into external factor-driven neurotoxicity and neurodegenerative pathogenesis.

Low-Dose Radiation Induces Alterations in Fatty Acid and Tyrosine Metabolism in the Mouse Hippocampus: Insights from Integrated Multiomics.

In recent years, there has been a drastic surge in neurological disorders with sporadic cases contributing more than ever to their cause. Radiation exposure through diagnostic or therapeutic routes often results in neurological injuries that may lead to neurodegenerative pathogenesis. However, the underlying mechanisms regulating the neurological impact of exposure to near-low doses of ionizing radiation are not known. In particular, the neurological changes caused by metabolomic reprogramming have not yet been elucidated. Hence, in the present study, C57BL/6 mice were exposed to a single whole-body X-ray dose of 0.5 Gy, and 14 days post-treatment, the hippocampus was subjected to metabolomic analysis. The hippocampus of the irradiated animals showed significant alterations in 15 metabolites, which aligned with altered tyrosine, phenylalanine, and alpha-linolenic acid metabolism and the biosynthesis of unsaturated fatty acids. Furthermore, a multiomics interaction network comprising metabolomics and RNA sequencing data analysis provided insights into gene-metabolite interactions. Tyrosine metabolism was revealed to be the most altered, which was demonstrated by the interaction of several crucial genes and metabolites. The present study revealed the regulation of low-dose radiation-induced neurotoxicity at the metabolomic level and its implications for the pathogenesis of neurological disorders. The present study also provides novel insights into metabolomic pathways altered following near-low-dose IR exposure and its link with neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

Regulation and tumor-suppressive function of the miR-379/miR-656 (C14MC) cluster in cervical cancer.

Cervical cancer (CC) is a key contributor to cancer-related mortality in several countries. The identification of molecular markers and the underlying mechanism may help improve CC management. We studied the regulation and biological function of the chromosome 14 microRNA cluster (C14MC; miR-379/miR-656) in CC. Most C14MC members exhibited considerably lower expression in CC tissues and cell lines in The Cancer Genome Atlas (TCGA) cervical squamous cell carcinoma and endocervical adenocarcinoma patient cohorts. Bisulfite Sanger sequencing revealed hypermethylation of the C14MC promoter in CC tissues and cell lines. 5-aza-2 deoxy cytidine treatment reactivated expression of the C14MC members. We demonstrated that C14MC is a methylation-regulated miRNA cluster via artificial methylation and luciferase reporter assays. C14MC downregulation correlated with poor overall survival and may promote metastasis. C14MC activation via the lentiviral-based CRISPRa approach inhibited growth, proliferation, migration, and invasion; enhanced G2/M arrest; and induced senescence. Post-transcriptional regulatory network analysis of C14MC transcriptomic data revealed enrichment of key cancer-related pathways, such as metabolism, the cell cycle, and phosphatidylinositol 3-kinase (PI3K)-AKT signaling. Reduced cell proliferation, growth, migration, invasion, and senescence correlated with the downregulation of active AKT, MYC, and cyclin E1 (CCNE1) and the overexpression of p16, p21, and p27. We showed that C14MC miRNA activation increases reactive oxygen species (ROS) levels, intracellular Ca2+ levels, and lipid peroxidation rates, and inhibits epithelial-mesenchymal transition (EMT). C14MC targets pyruvate dehydrogenase kinase-3 (PDK3) according to the luciferase reporter assay. PDK3 is overexpressed in CC and is inversely correlated with C14MC. Both miR-494-mimic transfection and C14MC activation inhibited PDK3 expression. Reduced glucose uptake and lactate production, and upregulation of PDK3 upon C14MC activation suggest the potential role of these proteins in metabolic reprogramming. Finally, we showed that C14MC activation may inhibit EMT signaling. Thus, C14MC is a tumor-suppressive and methylation-regulated miRNA cluster in CC. Reactivation of C14MC can be useful in the management of CC.

Advanced Computational Methods for Radiation Dose Optimization in CT.

BACKGROUND: In planning radiotherapy treatments, computed tomography (CT) has become a crucial tool. CT scans involve exposure to ionizing radiation, which can increase the risk of cancer and other adverse health effects in patients. Ionizing radiation doses for medical exposure must be kept "As Low As Reasonably Achievable". Very few articles on guidelines for radiotherapy-computed tomography scans are available. This paper reviews the current literature on radiation dose optimization based on the effective dose and diagnostic reference level (DRL) for head, neck, and pelvic CT procedures used in radiation therapy planning. This paper explores the strategies used to optimize radiation doses, and high-quality images for diagnosis and treatment planning. METHODS: A cross-sectional study was conducted on 300 patients with head, neck, and pelvic region cancer in our institution. The DRL, effective dose, volumetric CT dose index (CTDIvol), and dose-length product (DLP) for the present and optimized protocol were calculated. DRLs were proposed for the DLP using the 75th percentile of the distribution. The DLP is a measure of the radiation dose received by a patient during a CT scan and is calculated by multiplying the CT dose index (CTDI) by the scan length. To calculate a DRL from a DLP, a large dataset of DLP values obtained from a specific imaging procedure must be collected and can be used to determine the median or 75th-percentile DLP value for each imaging procedure. RESULTS: Significant variations were found in the DLP, CTDIvol, and effective dose when we compared both the standard protocol and the optimized protocol. Also, the optimized protocol was compared with other diagnostic and radiotherapy CT scan studies conducted by other centers. As a result, we found that our institution's DRL was significantly low. The optimized dose protocol showed a reduction in the CTDIvol (70% and 63%), DLP (60% and 61%), and effective dose (67% and 62%) for both head, neck, and pelvic scans. CONCLUSIONS: Optimized protocol DRLs were proposed for comparison purposes.

Extracellular vesicles as novel drug delivery systems to target cancer and other diseases: Recent advancements and future perspectives.

Extracellular vesicles (EVs) are lipid-bound vesicles produced into the extracellular space by cells. Apoptotic bodies (ApoBD), microvesicles (MVs), and exosomes are examples of EVs, which act as essential regulators in cell-cell communication in both normal and diseased conditions. Natural cargo molecules such as miRNA, messenger RNA, and proteins are carried by EVs and transferred to nearby cells or distant cells through the process of circulation. Different signalling cascades are then influenced by these functionally active molecules. The information to be delivered to the target cells depends on the substances within the EVs that also includes synthesis method. EVs have attracted interest as potential delivery vehicles for therapies due to their features such as improved circulation stability, biocompatibility, reduced immunogenicity, and toxicity. Therefore, EVs are being regarded as potent carriers of therapeutics that can be used as a therapeutic agent for diseases like cancer. This review focuses on the exosome-mediated drug delivery to cancer cells and the advantages and challenges of using exosomes as a carrier molecule.

Perineal body squamous cell carcinoma treated with radical radiotherapy - a case report.

Introduction: Perianal tumours are a rare site of malignancy, and tumours primarily involving the perineal body without vaginal and anal canal involvement are uncommon. Case summary: A 67-year-old woman presented with a lesion involving the perineum and rectovaginal septum without extension into vaginal or anorectal mucosa and with skip lesions in the vulva. Biopsy was confirmative of squamous cell carcinoma, with p16 positive. A complete metastatic workup with MRI of the pelvis and CECT thorax and abdomen was done. She was diagnosed with perianal carcinoma stage cT2N0M0 Stage II (American Joint Committee on Cancer 8th Edition of Cancer Staging) since the lesion reached the anal verge. Given the location of the tumour (perineal body), comorbidities and advanced age, she received radical radiotherapy with an intensity-modulated radiotherapy technique - 56 Gy in 28 fractions with the intention of organ preservation. The response assessment with MRI at 3 months showed a complete tumour response. She has been disease-free for 3 years and is on regular follow-ups. Conclusion: Isolated perineal body squamous cell carcinomas are unusual, and synchronous vulvar skip lesion makes this case unique. Radical radiotherapy achieved organ preservation with tumour control and minimal toxicity in an elderly frail patient.

Pelvic irradiation induces behavioural and neuronal damage through gut dysbiosis in a rat model.

Radiation exposure can cause gut dysbiosis and there is a positive correlation between gut microbial imbalance and radiation-induced side effects in cancer patients. However, the influence of radiation on the gut-brain axis (GBA) and its neurological consequences are not well understood. Therefore, this study aimed to investigate the impact of pelvic irradiation on gut microbiota and the brain. Sprague Dawley rats were irradiated with a single dose of 6 Gy, and faecal samples were collected at different time points (7 and 12-days post-irradiation) for microbial analysis. Behavioural, histological, and gene expression analysis were performed to assess the effect of microbial dysbiosis on the brain. The findings indicated alterations in microbial diversity, disrupted intestinal morphology and integrity, neuronal death-related brain changes, neuroinflammation and reduced locomotor activity. Hippocampal gene expression analysis also showed a reduced expression of neural plasticity-related genes. Overall, this study demonstrated that pelvic irradiation affects gut microbiota, intestinal morphology, integrity, brain neuronal maturation, neural plasticity gene expression, and behaviour.

Systematic Review on Diagnostic Reference Levels for Computed Tomography Examinations in Radiation Therapy Planning.

Background: In August 2017, the European Commission awarded the "European Study on Clinical Diagnostic Reference Levels (DRL) for X-ray Medical Imaging" project to the European Society of Radiology to provide up-to-date Diagnostic Reference Levels based on clinical indications. This work aimed to conduct an extensive literature review by analyzing the most recent studies published and the data provided by the National Competent Authorities to understand the current situation regarding Diagnostic Reference Levels based on clinical indications for Radiation Therapy Computed Tomography. Objective: To review the literature on established DRLs and methodologies for establishing Diagnostic reference levels in radiation therapy planning computed tomography (RTCT). Methods: Eligibility criteria: A cohort study (observational design) reporting DRLs in adult patients undergoing computed tomography (CT) for radiation therapy for the region head and neck or pelvis were included. The comprehensive literature searches for the relevant studies published between 2000 and 2021 were performed using PubMed, Scopus, CINHAL, Web of Science, and ProQuest. Results: Three hundred fifty-six articles were identified through an extensive literature search. Sixty-eight duplicate reports were removed. The title and abstract of 288 studies were assessed and excluded if they did not meet the inclusion criteria. Sixteen of 288 articles were selected for full-text screening (studies conducted between 2000 and 2021). Five articles were included in the review after the full-text screening. Conclusions: A globally approved standard protocol that includes scanning techniques, dose measurement method, and DRL percentile needs to be established to make a valuable and accurate comparison with international DRLs.

Increased Gene Expression of C1orf74 Is Associated with Poor Prognosis in Cervical Cancer.

C1orf74, also known as URCL4, has been reported to have higher expression and be associated with poor prognosis in lung adenocarcinoma patients, and its role in regulation of the EGFR/AKT/mTORC1 pathway has been recently elucidated. In the current study, we used publicly available data and experimental validation of C1orf74 gene expression and its association with prognosis in cervical cancer patients. qRT-PCR was performed using RNA from cervical cancer cell lines and twenty-five cervical cancer patients. Data from TNMplot revealed that mRNA expression of the C1orf74 gene in primary tumor tissues, as well as metastatic tissues from cervical cancer patients, was significantly higher compared to normal cervical tissues. HPV-positive tumors had higher expression of this gene compared to HPV-negative tumors. qPCR analysis also demonstrated higher expression of C1orf74 in HPV-positive cervical cancer cell lines and most cervical cancer patients. The promoter methylation levels of the C1orf74 gene in cervical cancer tissues were lower compared to normal cervical tissues (p < 0.05). Collectively, our study indicates that higher expression of the C1orf74 gene caused by hypomethylation of its promoter is associated with poor overall survival in cervical cancer patients. Thus, C1orf74 is a novel prognostic marker in cervical cancer.