In Response to "Acute Oral Mucositis During Hypo-Fractionated Radiation in Squamous Cell Carcinoma of Oral Cavity".

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Metastatic spinal cord compression: the Spinal Instability Neoplastic Score and early surgical intervention.

OBJECTIVES: To evaluate the value of Spinal Instability Neoplastic Score (SINS) in patients with spine metastasis who subsequently developed or did not develop metastatic spinal cord compression (MSCC). METHODS: In this single institutional retrospective descriptive observational study, of 589 patients with MSCC who were referred for radiotherapy, 34 patients (with 41 compression sites) met the inclusion criteria: availability of diagnostic MRI spine pre-development of MSCC (MRI-1) and at the time of MSCC development (MRI-2) (CordGroup).For comparison, NoCordGroup consisted of 152 patients (160 sites) treated with radiotherapy to spinal metastases. SINS was compared between the two groups. RESULTS: In CordGroup, the median interval between MRI-1 and MRI-2 was 11 weeks. The median SINS was 8 (range: 4-14) and 9 (range: 7-14) on MRI-1 and MRI-2, respectively. In NoCordGroup, the median SINS was 6 (range: 4-10). CONCLUSIONS: Our study showed a trend in difference in SINS value between the two groups. This difference should be a subject of future prospective research in this patient population with poor survival.

Reactive attachment disorder, disinhibited social engagement disorder, adverse childhood experiences, and mental health in an imprisoned young offender population.

BACKGROUND: A high proportion of young people in prison have a history of abuse and neglect, and/or of neurodevelopmental or psychiatric conditions.  Despite this, the only two conditions specifically associated with abuse and neglect, Reactive Attachment Disorder (RAD) and Disinhibited Social Engagement Disorder (DSED), have never been included as part of a comprehensive prevalence study. METHODS: A cross sectional study, in 110 male inmates aged 16 to 23, examined the prevalence of, and associations between, adverse childhood experiences (ACEs), neurodevelopmental and mental health conditions, including RAD and DSED. OUTCOMES: Virtually all of the young men (96 %) had one or more lifetime neurodevelopmental or mental health conditions, 85.5 % had a current condition, yet less than 3 % reported having received a mental health assessment in prison. High rates of RAD and/or DSED symptoms were found (53.6 %) and 74.5 % had experienced some form of abuse or neglect. INTERPRETATION: There is a high prevalence of ACEs, RAD/DSED, neurodevelopmental and other mental health conditions within this population. Comprehensive clinical assessments are required to ensure appropriate support and staff training is needed to ensure that the full implications of the high prevalence of neurodevelopmental and mental health conditions are understood as part of trauma informed care.

Bioengineering of a tumour-stroma 3D-tumouroid co-culture model of hypopharyngeal cancer.

Head and neck cancer (HNC) differs at anatomical sites and hypopharyngeal cancer (HPC) is a type of HNC. The non-surgical treatment option for advanced cases of HPC is radiotherapy (RT) with or without chemotherapy but survival is poor. Thus, new treatment approaches in combination with RT are essential. Yet, obtaining post-RT treated tumour specimens and lack of animal models with identical anatomical sites are the major translational research barriers. To overcome these barriers, for the first time, we have developed a tumour-stroma based in vitro three-dimensional (3D)-tumouroid co-culture model of HPC by growing FaDu and HS-5 cells together to mimic the complex tumour-microenvironment in a Petri dish. Before growing the cells together, imaging flow cytometry revealed distinct epithelial and non-epithelial characteristics of the cells. Growth rate of the 3D-tumouroid co-culture was significantly higher compared to the tumouroid monoculture of FaDu. Histology and morphometric analysis were done for the characterisation as well as the development of hypoxia was measured by CAIX immunostaining in this 3D-tumouroid co-culture. Taken together, this innovative in vitro 3D model of HPC resembles many features of the original tumour. The wider application of this pre-clinical research tool is in understanding newer combination (e.g. immunotherapy) treatment approaches with RT in HPC and beyond.

Hypofractionated (2.75 Gy per fraction) versus Conventionally Fractionated Primary Radiotherapy for T2N0M0 Carcinoma of the Glottis

Abstract 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.

Hypofractionated (2.75 Gy per fraction) versus Conventionally Fractionated Primary Radiotherapy for T2N0M0 Carcinoma of the Glottis.

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.

Every refuge has its price: Ostreobium as a model for understanding how algae can live in rock and stay in business.

Ostreobium is a siphonous green alga in the Bryopsidales (Chlorophyta) that burrows into calcium carbonate (CaCO3) substrates. In this habitat, it lives under environmental conditions unusual for an alga (i.e., low light and low oxygen) and it is a major agent of carbonate reef bioerosion. In coral skeletons, Ostreobium can form conspicuous green bands recognizable by the naked eye and it is thought to contribute to the coral's nutritional needs. With coral reefs in global decline, there is a renewed focus on understanding Ostreobium biology and its roles in the coral holobiont. This review summarizes knowledge on Ostreobium's morphological structure, biodiversity and evolution, photosynthesis, mechanism of bioerosion and its role as a member of the coral holobiont. We discuss the resources available to study Ostreobium biology, lay out some of the uncharted territories in Ostreobium biology and offer perspectives for future research.

Survival outcomes for patients with nasopharyngeal carcinoma in non-endemic region in the UK treated with intensity modulated based radiotherapy 65 Gy in 30 fractions ± weekly cisplatin chemotherapy.

Background: 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. Materials and methods: All consecutive 62 patients with histology proven non-metastatic nasopharyngeal carcinoma diagnosed between January 2009 to June 2019 were included in this retrospective analysis. Results: 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). Conclusion: 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.

Shrinkage of the non-malignant prostate gland volume after receiving incidental radiotherapy for rectal cancer.

Background: 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. Materials and methods: 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). Results: 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 cm3 [standard deviation (SD) 14.2] pre-radiotherapy to 31.3 cm3 (SD 13.0) post radiotherapy and this difference was significant (p = 0.0004). Conclusion: Radiotherapy 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.

A national survey of the radiotherapy dosimetrist workforce in the UK.

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.

Comprehensive Study of Antiretroviral Drug Permeability at the Cervicovaginal Mucosa via an In Vitro Model.

Modulation of drug transporter activity at mucosal sites of HIV-1 transmission may be exploited to optimize retention of therapeutic antiretroviral drug concentrations at target submucosal CD4+ T cells. Previously, we showed that darunavir was a substrate for the P-glycoprotein efflux drug transporter in colorectal mucosa. Equivalent studies in the cervicovaginal epithelium have not been reported. Here, we describe the development of a physiologically relevant model to investigate the permeability of antiretroviral drugs across the vaginal epithelium. Barrier properties of the HEC-1A human endometrial epithelial cell line were determined, in a dual chamber model, by measurement of transepithelial electrical resistance, immunofluorescent staining of tight junctions and bi-directional paracellular permeability of mannitol. We then applied this model to investigate the permeability of tenofovir, darunavir and dapivirine. Efflux ratios indicated that the permeability of each drug was transporter-independent in this model. Reduction of pH to physiological levels in the apical compartment increased absorptive transfer of darunavir, an effect that was reversed by inhibition of MRP efflux transport via MK571. Thus, low pH may increase the transfer of darunavir across the epithelial barrier via increased MRP transporter activity. In a previous in vivo study in the macaque model, we demonstrated increased MRP2 expression following intravaginal stimulation with darunavir which may further increase drug uptake. Stimulation with inflammatory modulators had no effect on drug permeability across HEC-1A barrier epithelium but, in the VK2/E6E7 vaginal cell line, increased expression of both efflux and uptake drug transporters which may influence darunavir disposition.

Postoperative radiotherapy delay in head and neck cancer patients undergoing major resection and free flap reconstruction.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 PORT >6 weeks after their surgery due to surgical complications. No patients experienced surgical complications during their PORT. CONCLUSION: In our experience, surgical aspects of free flap reconstructions do not appear to overtly delay or interrupt PORT.

Pre-Exposure to Stress-Inducing Agents Increase the Anticancer Efficacy of Focused Ultrasound against Aggressive Prostate Cancer Cells.

Despite the initial success in treatment of localized prostate cancer (PCa) using surgery, radiation or hormonal therapy, recurrence of aggressive tumors dictates morbidity and mortality. Focused ultrasound (FUS) is being tested as a targeted, noninvasive approach to eliminate the localized PCa foci, and strategies to enhance the anticancer potential of FUS have a high translational value. Since aggressive cancer cells utilize oxidative stress (Ox-stress) and endoplasmic reticulum stress (ER-stress) pathways for their survival and recurrence, we hypothesized that pre-treatment with drugs that disrupt stress-signaling pathways in tumor cells may increase FUS efficacy. Using four different PCa cell lines, i.e., LNCaP, C4-2B, 22Rv1 and DU145, we tested the in vitro effects of FUS, alone and in combination with two clinically tested drugs that increase Ox-stress (i.e., CDDO-me) or ER-stress (i.e., nelfinavir). As compared to standalone FUS, significant (p < 0.05) suppressions in both survival and recurrence of PCa cells were observed following pre-sensitization with low-dose CDDO-me (100 nM) and/or nelfinavir (2 µM). In drug pre-sensitized cells, significant anticancer effects were evident at a FUS intensity of as low as 0.7 kW/cm2. This combined mechanochemical disruption (MCD) approach decreased cell proliferation, migration and clonogenic ability and increased apoptosis/necrosis and reactive oxygen species (ROS) production. Furthermore, although activated in cells that survived standalone FUS, pre-sensitization with CDDO-me and/or nelfinavir suppressed both total and activated (phosphorylated) NF-κB and Akt protein levels. Thus, a combined MCD therapy may be a safe and effective approach towards the targeted elimination of aggressive PCa cells.

The role of combining immunotherapy with primary (Chemo)radiotherapy in curative treatment settings of the head and neck cancer.

The introduction of immunotherapy into the radical management of head and neck cancer (HNC) is a fast moving phenomenon, which is constantly developing. Although now established in the management of recurrent and metastatic disease in HNC, its use in radical treatment is being investigated in a whole spectrum of clinical trials looking at which immune altering agents give the best results, which can be added safely to radiotherapy, chemotherapy, and chemoradiotherapy for greatest efficiency and when the most appropriate time to add these agents is in the neoadjuvant, concurrent on adjuvant settings. These multiple questions produce a complex matrix for HNC investigators and this article brings together the existing evidence and contemporary trials going on with immunotherapy in HNC, giving an up to date snapshot of present investigations and near future directions for further research.