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Introduction Radiotherapy provides excellent outcome in early stage glottic cancer; however, the optimal radiotherapy dose fractionation remains unknown. Objective To investigate the outcome of patients with T2N0M0 treated with either hypofractionated (HypoFxn) or conventionally fractionated radical (ConFxn) radiotherapy. Methods According to our institutional protocol, patients with T2N0M0 glottic cancer can be treated either with ConfFxn or HypoFxn radiotherapy, as per clinician's and patient's choice, following shared decision making discussing the advantages and disadvantages of both modalities. A total of 77 patients with T2N0M0 squamous cell carcinoma of glottis treated with either HypoFxn 55Gy in 20 fractions (n = 19) or ConFxn 63 to 65Gy in 30 fractions (n = 58) were included. Results With median follow-up of 3.4 years, there was no significant difference in disease-free survival (median: HypoFxn = 65.2 months, and ConFxn = 75.3 months; p = 0.874), local recurrence free survival rates (median: HypoFxn = 78.8 months vs. ConFxn = 81.2 months; p = 0.274), and overall survival (median: HypoFxn = 65.9 months vs. ConFxn = 67.7 months; p = 0.532). Elective neck irradiation was given to 43 patients, all in the ConFxn group, and this was associated with poorer local control (p = 0.027). The use of radiotherapy modality, three-dimensional conformal radiotherapy (3DRT) versus intensity modulated radiotherapy (IMRT), was not a prognostic factor (p = 0.36). In the HypoFxn group, grade III acute dysphagia requiring nasogastric tube was 16%, compared with 25% in the ConFxn group (p = 0.446). Conclusion HypoFxn radiotherapy provides a comparable treatment outcome with acceptable toxicity. The addition of prophylactic irradiation of the neck lymph nodes has no impact on regional control.

Delays to postoperative radiotherapy (PORT) are frequent and associated with poorer oncologic outcomes in head and neck cancer (HNC) patients. Free flap patients have been suggested as the most at-risk group. Thus, PORT delivery experienced by HNC patients who required a free flap reconstruction was analysed, identifying reasons for the delays if any.A retrospective analysis of a single tertiary unit's PORT delivery to HNC patients undergoing major resection followed by free flap reconstruction between 2017 and 2020.Eighty-seven patients were identified. Thirty-two patients received PORT within 6 weeks of their surgery date. Reasons for the delays could be categorised into surgery-derived, system-derived and patient-derived reasons. Five patients (5.74%) received PORT6 weeks after their surgery due to surgical complications. No patients experienced surgical complications during their PORT.In our experience, surgical aspects of free flap reconstructions do not appear to overtly delay or interrupt PORT.

Objectives: To undertake a national survey of the Radiotherapy Dosimetrist workforce within the UK; examining different attributes and experiences, comparing results with published evidence within the literature. Methods: A national, anonymised survey was undertaken between Dec 2020 and end of Feb 2021; employing a mixed-methods approach and blend of closed, open-ended answer choices and free-text comments. Questions included range of training routes and job titles; registration status; job tasks and engagement with Continuing Professional Development (CPD). Results A total of 223 individuals responded. Nearly half were trained via therapeutic radiography; approximately, a fifth through a clinical technologist/physics routes. Most (70%) had Dosimetrist in their job title. Nearly 70% were statutorily registered, and almost a fifth were in the voluntary register of Clinical Technologists. Most job tasks were in treatment planning – with 57% spending over 70% of their time there. Most notably, 29% were not involved in any CPD scheme. No published evidence showed the same aspects identified here. Conclusions: Our survey showed a unique profile of the Radiotherapy Dosimetrist workforce in the UK, with a variety of training routes and statutory registration status. Nearly, a third were not engaged in a CPD scheme – adding to the current discussion that perhaps all Dosimetrists should be statutorily registered, for ensuring safe and effective clinical practice. Advances in knowledge: A novel and unique national survey of Dosimetrists working in Radiotherapy in the UK is presented, leading to new insights into current training routes, registration status, job tasks and CPD engagement and needs.

OBJECTIVES To analyse the oncological outcomes following primary Transoral Robotic Surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC). DESIGN Observational case series. SETTING Tertiary centre; first TORS practice to commence in the UK. PARTICIPANTS All consecutive patients undergoing primary TORS with curative intent, with or without adjuvant treatment. MAIN OUTCOME MEASURES Descriptive analysis of patient and tumour pathology variables. Survival outcomes: Overall, Disease-Specific, Progression-Free and Locoregional control. RESULTS The cohort comprised of 120 patients undergoing TORS with minimum 12-month follow-up data and the following characteristics: mean age 58 years, 91 males (76%), 78 tonsil (65%) and 34 base of tongue primaries (28%), 89% HPV-related OPSCC. The surgical pathology revealed 14 (12%) with positive margins, 19 (16%) had close margins

ObjectiveTo examine the patterns of care for octogenarian head and neck cancer patients.MethodsAll newly diagnosed patients aged 80 years or older, who presented at our centre between June 2018 and October 2020, were included.ResultsThe total number of patients was 42. The median Charlson Comorbidity Index was 5 (range, 4–9). The larynx was the most common subsite (n = 12). Twenty-nine patients (66 per cent) were diagnosed at disease stage IV. Squamous cell carcinoma was the most common histology (86 per cent). Twenty-six patients (62 per cent) had radical treatment and 16 (38 per cent) had palliative treatment. The estimated six-month and one-year overall survival rates for the radical and palliative treatment cohorts were 92.3 per cent and 42.9 per cent (p = 0.001) and 65.4 per cent and 15.4 per cent (p = 0.003), respectively.ConclusionThis study provides useful information on octogenarian patients with head and neck cancer. This information may help in conducting prospective studies, especially those focusing on older patients with head and neck cancer, in order to define the ideal care of this patient population.

During the Covid-19 pandemic, it was postulated that there might be a delay in cancer patients` presentation, stage migration, changes in management leading to excess cancer mortality [1]. However, there is a paucity of real-time objective data to support this, particularly in HNC. In our HNC multidisciplinary team (MDT), approximately 300 new patients present annually. The purpose of this observational study was to assess the impact of Covid-19 on the presentation, stage and management pattern on newly presented HNC patients during the pandemic era.

Background Existing therapeutic interventions to treat diabetes are well known, yet the majority of people with diabetes do not consistently achieve blood glucose targets (even individual therapy targets) for optimal health, despite the large range of treatment options available. Such outcomes have remained stubbornly poor for decades with Methods A multi-centre, parallel group, individually randomised trial comparing consultation duration in adults with type 1, type 2 or pre-diabetes using the Spotlight Consultations pre-clinic assessment compared to usual care in the Spotlight-AQ study. Two hundred adults with type 1, type 2 or pre-diabetes attending routine care outpatient appointments across up to ten participating sites will be invited to participate. Intervention An outpatient pre-clinic intervention delivered within 1 week prior to scheduled routine outpatient appointment. Primary outcome measure Duration of routine outpatient consultation. Secondary outcome measures Functional health status Diabetes distress Depression Treatment satisfaction Impact on self-care behaviours HCP burnout HCP treatment satisfaction and burden Hypoglycaemia (time less than 70mg/dL) Hyperglycaemia (time above 180 mg/dL) Change in weight Change in HbA1c Cost effectiveness of intervention Discussion Results from the study will provide valuable insights into patient-professional communication practices within routine care and recommendations will be made, as necessary, for improvements to that. If the intervention is shown to be clinically and cost-effective, the feedback from participants and healthcare professionals will be used to make any improvements prior to its deployment to support improved communication and associated health outcomes. Ethics and dissemination The trial was approved by the Wales REC7 Research Ethics Committee (21/WA/0020). Results will be disseminated through national and international conferences, scientific journals, newsletters, magazines and social media. Target audiences include consultants and other clinicians in diabetes, and medical professionals or scientists overall. Trial registration ISRCTN15511689. Registered on 10 November 2021

Nasopharyngeal carcinoma (NPC) is rare in the UK. The aim of the current study was to investigate survival outcomes for patients with NPC treated with (chemo)radiotherapy using 65 Gy in 30 fractions in a non-endemic region.All consecutive 62 patients with histology proven non-metastatic nasopharyngeal carcinoma diagnosed between January 2009 to June 2019 were included in this retrospective analysis.Median age was 59 years (range:19-81). The majority of patients had stage III disease (66.1%). Induction chemotherapy was given in 21% of patients and 82.3% of patients received concomitant systemic therapy. All patients were treated with 65 Gy in 30 fractions. There was disease recurrence in 17.4% patients. The 5-year disease-free, disease-specific and overall survival were 81.9%, 79.2% and 76.4%, respectively. On univariate analysis, disease recurrence was associated with N-stage (p = 0.047) and overall stage group (p = 0.023).To the best of authors' knowledge, this is the first report of the use of 65 Gy in 30 fractions of radiotherapy ± weekly cisplatin chemotherapy in NPC in a real-world setting. Our results are comparable to that from other non-endemic regions of the world using different dose fractionation of (chemo)radiotherapy. Future randomised control trials are warranted to compare various dose fractionations in these settings.

Clinical trials have demonstrated partial protection against HIV-1 infection by vaginal microbicide formulations based on antiretroviral (ARV) drugs. Improved formulations that will maintain sustained drug concentrations at viral target sites in the cervicovaginal mucosa are needed. We have previously demonstrated that treatment of cervicovaginal cell lines with ARV drugs can alter gene expression of drug transporters, suggesting that the mucosal disposition of ARV drugs delivered vaginally can be modulated by drug transporters. This study aimed to investigate in vivo modulation of drug transporter expression in a nonhuman primate model by tenofovir and darunavir released from film formulations. Cervicovaginal tissues were collected from drug-naive macaques and from macaques vaginally treated with film formulations of tenofovir or darunavir. Drug release in vaginal fluid as well as drug absorption in cervicovaginal tissues and lymph nodes were verified by mass spectrometry. The effects of exposure to drugs on the expression of transporters relevant to ARV drugs were evaluated by quantitative PCR. We showed expression in cervicovaginal tissue of drug-naive macaques of transporters important for distribution of ARV drugs, albeit at lower levels compared to human tissue for key transporters including P-glycoprotein. Concentrations of tenofovir and darunavir well above the EC50 values determined in vitro were detected in vaginal fluid and vaginal tissues of macaques treated with drug-dissolving films over 24 h and were also comparable to those shown previously to modulate drug transporter expression. Accordingly, Multidrug Resistance associated Protein 2 (MRP2) in cervicovaginal tissue was upregulated by both tenofovir and darunavir. The two drugs also differentially induced and/or inhibited expression of key uptake transporters for reverse transcriptase inhibitors and protease inhibitors. The lower expression of key transporters in macaques may result in increased retention of ARV drugs at the simian cervicovaginal mucosa compared to the human mucosa and has implications for translation of preclinical data. Modulation of drug transporter expression by tenofovir and darunavir points to the potential benefit of MRP2 inhibition to increase ARV drug penetration through the cervicovaginal epithelium.

The purpose of this study was to assess the impact of coincidental radiotherapy on the volume of the non-malignant prostate gland in rectal cancer patients treated with neo-adjuvant radiotherapy.In this retrospective analysis, thirty male patients with rectal cancer who had neoadjuvant radiotherapy met the inclusion criteria. These patients had pre-treatment magnetic resonance imaging (MRI) and at least one post-treatment MRI of the pelvis and the whole of their prostate volume received the full prescribed radiotherapy dose; 45 Gy in 25 fractions (n = 22), 45 Gy in 20 fractions (n = 4) and 25 Gy in 5 fractions (n = 4).The median age of this patient cohort was 66 years (range: 30-87). With a median interval between pre-treatment MRI and first MRI post-treatment of 2 months (range: 1-11), the mean prostate volume reduced from 36.1 cmRadiotherapy may cause shrinkage in volume of normal (non-malignant) prostate. Further research is required in this field, since these results may be of some comfort to men contemplating the consequences of radiotherapy on their quality of life. The authors suggest recording flow-rate and international prostate symptom score (IPSS) during rectal radiotherapy as a next step.

Introduction: Existing therapeutic interventions to treat diabetes are well known, yet the majority of people with diabetes do not consistently achieve blood glucose targets (even individual therapy targets) for optimal health, despite the large range of treatment options available. Such outcomes have remained stubbornly poor for decades with Participants: Adults with type 1, type 2 or pre-diabetes attending routine care outpatient appointments.Design: A multi-centre, parallel group, individually randomised trial comparing consultation duration in adults with type 1, type 2 or pre-diabetes using the Spotlight Consultations pre-clinic assessment compared to usual care in the Spotlight-AQ study.Intervention: An outpatient pre-clinic intervention delivered within one week prior to scheduled routine outpatient appointment.Sample size: 200 recruited across up to 10 sites.Primary outcome measure: Duration of routine outpatient consultation.Secondary outcome measures:· Functional health status· diabetes distress · depression· treatment satisfaction· impact on self-care behaviours· HCP burnout· HCP treatment satisfaction and burden · hypoglycaemia (time less than 70mg/dL)· hyperglycaemia (time above 180 mg/dL)· Change in weight · Change in HbA1c · Cost effectiveness of interventionEthics and dissemination: The trial was approved by the Wales REC7 Research Ethics Committee (21/WA/0020). Results will be disseminated through national and international conferences, scientific journals, newsletters, magazines and social media. Target audiences include consultants and other clinicians in diabetes, and medical professionals or scientists overall. Trial Registration: ISRCTN15511689

Gerhard Von Rad Defended The Importance Of The Old Testament For Christians In The Face Of Nazi Pressure. Reacting To The Sterility Of A Religionsgeschichte Approach, He Was A Part Of The Biblical Theology Movement And Sought To Set Forth The Theological Material Of The Old Testament In Roughly Historical Order As A Summary Of Israelite Faith. Attempting To Set Forth The “saving Acts Of God,” His Equivocal Use Of The Category “history” Failed To Bridge His Modernist Assumptions That Reality Is Unbreachably Divided Into The Phenomenal And The Noumenal. Though A Number Of His Assumptions About Wisdom Literature Have Since Been Discredited, Von Rad Strove To Approach Old Testament Wisdom On Its Own Terms, With Poetic Sensitivity, Respect, And Deep Appreciation. KEYWORDS

Background: Burnout in people with diabetes and healthcare professionals (HCPs) is at an all-time high. Spotlight AQ, a novel “smart” adaptive patient questionnaire, is designed to improve consultations by rapidly identifying patient priorities and presenting these in the context of best-practice care pathways to aid consultations. We aimed to determine Spotlight AQ’s feasibility in routine care. Materials and Methods: The Spotlight prototype tool was trialed at three centers: two UK primary care centers and one US specialist center (June-September 2020). Participants with type 1 (T1D) or type 2 diabetes (T2D) completed the questionnaire prior to their routine consultations. Results were immediately available and formed the basis of the clinical discussion and decision-making within the clinic visit. Results: A convenience sample of 49 adults took part, n=31 T1D, ( n=18 female); and n=18 T2D ( n=10 male, n=4 female, n=4 gender unreported). Each identified two priority concerns. “Psychological burden of diabetes” was the most common priority concern (T1D n = 27, 87.1%) followed by “gaining more skills about particular aspects of diabetes” (T1D n=19, 61.3%), “improving support around me” ( n=8, 25.8%) and “diabetes-related treatment issues” ( n=8, 25.8%). Burden of diabetes was widespread as was lack of confidence around self-management. Similarly, psychological burden of diabetes was the primary concern for participants with T2D ( n=18,100%) followed by “gaining more skills about aspects of diabetes” ( n=7, 38.9%), “improving support around me” ( n=7, 38.9%) and “diabetes-related treatment issues” ( n=4; 22.2%). Conclusions: Spotlight AQ is acceptable and feasible for use in routine care. Gaining more skills and addressing the psychological burden of diabetes are high-priority areas that must be addressed to reduce high levels of distress.

Introduction In head and cancer (HNC), osteoradionecrosis (ORN) is one of the most significant complications of radiotherapy (RT). With an absence of effective non-surgical treatment, prevention of the development of ORN is the best approach. Purpose To identify the risk factors for the development of ORN in HNC. Materials and methods Records of 1118 patients with HNC treated with radical RT (≥55 Gy) from January 2010 to December 2019 were reviewed. After applying the exclusion criteria, 935 patients were included in the final analysis. In patients with confirmed ORN, exact RT doses were mapped in the origin of ORN. Results In total, 91 patients were found to have ORN (9.7%) with a median time of 8 months (range: 3-89 months) to ORN development. Smoking, having a primary site in the oropharynx, bone surgery before adjuvant RT, the addition of concurrent chemotherapy, the presence of xerostomia, dental extraction pre-RT, the time ≤20 days between dental extraction and start of RT and receiving >55 Gy RT dose were significant factors for ORN development. Conclusion This comprehensive analysis including the precise RT dose mapping has shown the risk factors for the development of ORN. In practice, every effort should be made to avoid these risk factors without compromising the oncology treatment. The findings of this analysis may provide a basis for future prospective research on this topic.

Introduction In radiotherapy (RT) for head and neck cancer (HNC), dental morbidity is significant and it may result in loss of the dentition following treatment. Aims The aim of this clinical study is to identify the incidence of tooth loss over time and correlate this to the RT dose and various risk factors in patients with HNC treated with radical RT. Design A retrospective observational study. Materials and methods The records of 1,118 patients with HNC treated with radical or adjuvant RT from January 2010 to December 2019 were analysed. After applying strict inclusion criteria, 78 patients with 1,566 individual tooth data were selected. RT dose mapping was performed for each tooth. Results A total of 253 teeth (16.2%) were extracted. The following risk factors were significant: gender (p = 0.0001), xerostomia (p

Numerous trials have been launched over the prior decade examining the safety and efficacy of therapy de-escalation in human papillomavirus (HPV)-associated oropharyngeal cancer (OPC). Because no summative assessment of these prospective trials exists to date, we systematically reviewed the outcomes and toxicities associated with therapy de-intensification for this population. PRISMA-guided systematic PubMed searches (along with articles known to the authors and references thereof) were performed for prospective studies reporting clinical outcomes and/or toxicities of de-intensified RT and/or systemic therapy (with or without surgery), exclusively for HPV-associated OPC. Ten prospective studies were analyzed. Performing a meta-analysis was not entirely possible owing to the heterogeneity of treatment paradigms and the lack of2 studies for most paradigms; however, because just one paradigm (induction chemotherapy followed by reduced-dose RT and/or systemic therapy) had 4 associated articles, an exploratory meta-analysis was conducted for that subset. Two trials of dose-reduced concurrent chemoradiotherapy (60 Gy/weekly cisplatin) demonstrated 3-year distant metastasis-free survival and overall survival (OS) ranging from 91 to 100% and 95%, respectively; acute grade 3+ mucositis and dysphagia occurred in 33-35% and 21-39%, respectively. In the four trials of induction chemotherapy (platinum/taxane-based) followed by dose-reduced RT, 2-year progression-free and OS ranged from 80 to 95% and 83 to 98%, respectively; acute grade 3+ dysphagia, dermatitis, and mucositis ranged from 9 to 15%, 7 to 20%, and 9 to 30% (excluding one outlier), respectively. For these four trials, the exploratory meta-analysis showed a pooled 2-year PFS and OS of 89% (95% confidence interval, 80-96%) and 96% (92-99%). The pooled rates of grade ≥3 dysphagia, dermatitis, and mucositis were 13% (7-19%), 9% (5-14%), and 28% (9-53%). However, there was significant heterogeneity in the 2-year PFS (I

Background The long-term effect of concurrent chemoradiation on voice outcomes in the context of non-laryngeal head and neck cancer is not established. Methods A prospective, observational study to evaluate the voice quality in disease-free patients receiving concurrent chemoradiation for advanced non-laryngeal squamous cell carcinoma of the upper aerodigestive tract. Voice assessment occurred at four distinct time-points: pretreatment, 3, 12 and 92.6 months (mean) post-treatment in 34, 21 and nine patients, respectively. The authors used a combination of subjective (VoiSS questionnaire), expert rater-assessed (GRBAS scale) and acoustic analysis of the fundamental frequency to assess voice outcomes. Ethical approval was obtained from the United Kingdom National Research Ethics Service. Results Both the VoiSS impairment and GRBAS domains continued to deteriorate over time from pre-treatment to 92.6 months post-treatment (P = 0.03). There was a strong correlation between increase in total VoiSS and GRBAS scores (r = 0.93). Acoustic analysis demonstrated no statistically significant variation in fundamental frequency. Conclusion Radiation therapy for advanced non-laryngeal head and neck has a significant, deleterious effect on voice, which is apparent up to eight years post-treatment.

Diagnostic tonsillectomy is rarely an oncologic operation owing to close or positive margins. The standard of care is for further treatment to the primary site, typically with adjuvant radiotherapy. 14 patients with close or positive margins following a diagnostic tonsillectomy underwent transoral robotic surgery (TORS) and lateral oropharyngectomy; five patients with the longest follow-up had their excision specimens examined with a step serial sectioning technique (SSS). Conventional histopathological examination of the TORS resection specimens did not demonstrate residual carcinoma in 13 patients, confirmed by examination using SSS in 5 patients. There were no post-operative complications or long-term functional deficit. Seven patients received surgery alone with 100% overall and disease specific survival, respectively (median follow-up 27.5 months; range 5.2–50.4). This prospective study suggests that TORS lateral oropharyngectomy alone is an oncologically safe treatment when close or positive margins are identified on diagnostic tonsillectomy in HPV-positive SCC.

Background and purpose: Magnetic Resonance (MR)-only radiotherapy requires geometrically accurate MR images over the full scanner Field of View (FoV). This study aimed to investigate the repeatability of distortion measurements made using a commercial large FoV phantom and analysis software and the sensitivity of these measurements to small set-up errors. Materials and methods: Geometric distortion was measured using a commercial phantom and software with 2D and 3D acquisition sequences on three different MR scanners. Two sets of repeatability measurements were made: three scans acquired without moving the phantom between scans (single set-up) and five scans acquired with the phantom re-set up in between each scan (repeated set-up). The set-up sensitivity was assessed by scanning the phantom with an intentional 1 mm lateral offset and independently an intentional 1° rotation. Results: The mean standard deviation of distortion for all phantom markers for the repeated set-up scans was

Magnetic resonance imaging (MRI) offers superior soft-tissue contrast as compared with computed tomography (CT), which is conventionally used for radiation therapy treatment planning (RTP) and patient positioning verification, resulting in improved target definition. The 2 modalities are co-registered for RTP; however, this introduces a systematic error. Implementing an MRI-only radiation therapy workflow would be advantageous because this error would be eliminated, the patient pathway simplified, and patient dose reduced. Unlike CT, in MRI there is no direct relationship between signal intensity and electron density; however, various methodologies for MRI-only RTP have been reported. A systematic review of these methods was undertaken. The PRISMA guidelines were followed. Embase and Medline databases were searched (1996 to March, 2017) for studies that generated synthetic CT scans (sCT)s for MRI-only radiation therapy. Sixty-one articles met the inclusion criteria. This review showed that MRI-only RTP techniques could be grouped into 3 categories: (1) bulk density override; (2) atlas-based; and (3) voxel-based techniques, which all produce an sCT scan from MR images. Bulk density override techniques either used a single homogeneous or multiple tissue override. The former produced large dosimetric errors (>2%) in some cases and the latter frequently required manual bone contouring. Atlas-based techniques used both single and multiple atlases and included methods incorporating pattern recognition techniques. Clinically acceptable sCTs were reported, but atypical anatomy led to erroneous results in some cases. Voxel-based techniques included methods using routine and specialized MRI sequences, namely ultra-short echo time imaging. High-quality sCTs were produced; however, use of multiple sequences led to long scanning times increasing the chances of patient movement. Using nonroutine sequences would currently be problematic in most radiation therapy centers. Atlas-based and voxel-based techniques were found to be the most clinically useful methods, with some studies reporting dosimetric differences of