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Pembrolizumab has received approval in the UK as first-line monotherapy for recurrent and/or metastatic HNSCC (R/M HNSCC) following the results of the KEYNOTE-048 trial, which demonstrated a longer overall survival (OS) in comparison to the EXTREME chemotherapy regimen in patients with a combined positive score (CPS) ≥1. In this article, we provide retrospective real-world data on the role of pembrolizumab monotherapy as first-line systemic therapy for HNSCC across 18 centers in the UK from March 20, 2020 to May 31, 2021. 211 patients were included, and in the efficacy analysis, the objective response rate (ORR) was 24.7%, the median progression-free survival (PFS) was 4.8 months (95% confidence interval [CI]: 3.6-6.1), and the median OS was 10.8 months (95% CI 9.0-12.5). Pembrolizumab monotherapy was well tolerated, with 18 patients having to stop treatment owing to immune-related adverse events (irAEs). 53 patients proceeded to second-line treatment with a median PFS2 of 10.2 months (95% CI: 8.8-11.5). Moreover, patients with documented irAEs had a statistically significant longer median PFS (11.3 vs. 3.3 months; log-rank p value = <.001) and median OS (18.8 vs. 8.9 months; log-rank p value <.001). The efficacy and safety of pembrolizumab first-line monotherapy for HNSCC has been validated using real-world data., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Introduction/background: Patients receiving treatment for head and neck cancer (HNC) with curative intent, will potentially undergo primary or adjuvant radiation therapy (RT). These patients require supportive management from an extended multi-disciplinary team, to manage the severe toxicities and distress that a course of treatment can bring. A survey was designed to determine if there were changes in the experience of HNC patients attending for radical RT, from the beginning to the end of their treatment course. During the conduct of the survey the COVID-19 pandemic began. As a result cancer services were adapted to keep patients receiving treatment protected from the virus, while continuing to treat their malignant disease. This enabled a comparison of HNC patient experiences pre-pandemic (PP) and during the pandemic (DP). The study aimed to assess the impact of changes in treatment logistics, implemented as a result of the COVID-19 pandemic, on the patient experience, analysing and comparing how well patients understood the information provided to them, their level of distress and anxiety during treatment, and their overall satisfaction with the experience., Methods: Eligible patients were receiving radical RT for HNC of any sub-site or histological type. Identical, anonymous surveys were distributed to patients at week 1 and the final week of RT. The initial PP questionnaire (distributed December 2019 to 11 th March 2020) contained 22 questions with space for free text. The questionnaire was amended DP to include 6 additional COVID-19 related questions (distributed June to November 2020)., Results: One hundred and eighty two surveys were returned; 95 (52%) PP and 87 (48%) DP. Patients were moderately distressed from wearing the immobilisation mask towards the end of treatment DP with a statistically significant difference in the final week, median (IQR) values of 1 (0-4) PP and 2 (1-6) DP, p=0.024. Patients reported increased distress by attending daily for treatment by the final week of RT DP, with a PP and DP median of 1 (0-3) and 2 (1-4) respectively, p=0.039. Patients reporting increased levels of distress about attending for RT also reported high levels of anxiety about COVID-19 (r=0.40, p=0.005). COVID-19 anxiety score displayed a weak inverse association with overall treatment satisfaction score (r=-0.28, p=0.008)., Conclusion: Despite the adapted COVID-19 working practices implemented and the challenges a course of head and neck RT entails, patients reported a positive experience attending for treatment, both PP and DP., (Copyright © 2024. Published by Elsevier Inc.)

Background: Radiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience., Methods: This study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival., Discussion: This study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone., Trial Registration: Clinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023., (© 2024. The Author(s).)

In 25% of patients presenting with embolic stroke, a cause is not determined. Atrial fibrillation (AF) is a commonly identified mechanism of stroke in this population, particularly in older patients. Conventional investigations are used to detect AF, but can we predict AF in this population and generally? We performed a systematic review to identify potential predictors of AF on 12-lead electrocardiogram (ECG)., Method: We conducted a search of EMBASE and Medline databases for prospective and retrospective cohorts, meta-analyses or case-control studies of ECG abnormalities in sinus rhythm predicting subsequent atrial fibrillation. We assessed quality of studies based on the Newcastle-Ottawa scale and data were extracted according to PRISMA guidelines., Results: We identified 44 studies based on our criteria. ECG patterns that predicted the risk of developing AF included interatrial block, P-wave terminal force lead V1, P-wave dispersion, abnormal P-wave-axis, abnormal P-wave amplitude, prolonged PR interval, left ventricular hypertrophy, QT prolongation, ST-T segment abnormalities and atrial premature beats. Furthermore, we identified that factors such as increased age, high CHADS-VASC, chronic renal disease further increase the positive-predictive value of some of these parameters. Several of these have been successfully incorporated into clinical scoring systems to predict AF., Conclusion: There are several ECG abnormalities that can predict AF both independently, and with improved predictive value when combined with clinical risk factors, and if incorporated into clinical risk scores. Improved and validated predictive models could streamline selection of patients for cardiac monitoring and initiation of oral anticoagulants., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, we focused on understanding key storage traits of seeds from Macrozamia fraseri , an unusual though important species that is impacted by mining. To support current restoration activities, large amounts of seed from M. fraseri have been regularly collected and stored for up to 8 years under standard seed banking conditions (5°C and 20% relative humidity), though in situ recruitment from directly sown seed is poor. To investigate the underlying constraints to germination on demand, we set out to assess the viability of M. fraseri seeds that had been stored in a restoration seed bank from 6 to 66 months. Seed moisture content (MC) (fresh weight basis) was also determined for seeds with different storage histories to ascertain whether M. fraseri seeds display traits (i.e. high MC) that might suggest non-orthodox seed storage behaviour. The youngest seed accession (6 months old) was found to have a high MC (45.8 ± 5.4%-fresh weight basis), and >50% viability. In comparison, older (>30 months old) accessions were observed to have a marked reduction in both seed MC (10-35% MC) and viability (0-29.4%). While preliminary, we conclude that M. fraseri seeds appear to lose viability during conventional storage with younger accessions displaying both a higher seed MC and viability, compared to accessions stored for longer. Given the significance of these results, future research activities are recommended to better understand the interplay between seed MC and storage environment and how this relates to the seasonally dry Mediterranean climate where this species naturally occurs. As well, storage and propagation approaches are proposed to increase success when using M. fraseri for conservation and restorative activities., Competing Interests: All authors acknowledge that regarding this manuscript there is no conflict of interest to declare., (© The Author(s) 2023. Published by Oxford University Press and the Society for Experimental Biology.)

Background and Aim: The aim of this study was to evaluate the long-term safety of the omission of immediate neck dissections (IND) in patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) achieving a less than complete nodal response on 12-week FDG PET-CT., Material and Methods: Patients with HPV-positive, node-positive HNSCC that were treated with radical (chemo) radiotherapy (RT) between January 2013 and September 2019 were identified. PET-CT responses were classified as complete (CR), incomplete (ICR) or equivocal (EQR) nodal responses. Clinical outcomes were obtained., Results: 347 patients were identified. Median follow-up was 43.9 (IQR, 30.8-61.2) months. 62.8% (218/347) achieved a CR, 23.4% (81/347) EQR and 13.8% (48/347) ICR nodal response. 70 of 81 (86.4%) patients with an EQR and 25 of 48 (52.1%) with an ICR had no residual disease during follow up (a pathologically negative ND if surgery undertaken or no subsequent neck or distant relapse clinically/radiologically). Median survival of the EQR and CR groups were not reached, and despite the omission of IND in 95% of the EQR group there was no statistically significant differences in overall survival (OS) between the groups, p = 1.0. Median survival of ICR was not reached. However, OS for ICR group was significantly worse than that of CR, and EQR, both p < 0.001., Conclusion: The omission of IND in those achieving an EQR nodal response does not compromise long-term survival. This supports the safety of extended surveillance in patients with HPV-positive disease and an EQR on 12-week FDG PET-CT., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: Following resection of pancreatic cancer, risk of positive margins and local recurrence remain high, especially for borderline-resectable pancreatic cancer (BRPC). We aimed to establish the maximum tolerated dose of a margin-intensified five-fraction stereotactic body radiotherapy (SBRT) regimen designed to treat the region at risk., Materials and Methods: We conducted a prospective multicentre phase-1 rolling-six dose-escalation study. BRPC patients received pre-operative SBRT, with one dose to the primary tumour and an integrated boost to the region where tumour was in contact with vasculature. Four dose-levels were proposed, with starting dose 30 Gy to primary PTV and 45 Gy to boost volume (PTV&#95;R), in five daily fractions. Primary endpoint was maximum tolerated dose (MTD), defined as highest dose where zero of three or one of six patients experienced dose-limiting toxicity (DLT)., Results: Twelve patients were registered, eleven received SBRT. Radiotherapy was well tolerated with all treatment completed as scheduled. Dose was escalated one level up from starting dose without encountering any DLT (prescribed 32.5 Gy PTV, 47.5 Gy PTV&#95;R). Nine serious adverse reactions or events occurred (seven CTCAE Grade 3, two Grade 4). Two patients went on to have surgical resection. Median overall survival for SBRT patients was 8.1 months. The study closed early when it was unable to recruit to schedule., Conclusion: Toxicity of SBRT was low for the two dose-levels that were tested, but MTD was not established. Few patients subsequently underwent resection of pancreatic tumour after SBRT, and it is difficult to draw conclusions regarding the safety or toxicity of these therapies in combination., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Oesophageal cancer remains a common cause of cancer mortality worldwide. Increasingly, oncology centres are treating an older population and comorbidities may preclude multimodality treatment with chemoradiotherapy (CRT). We review outcomes of radical radiotherapy (RT) in an older population treating squamous cell carcinoma (SCC) oesophagus., Methods: Patients over 65 years receiving RT for SCC oesophagus between 2013 and 2016 in the West of Scotland were identified. Kaplan-Meier and Cox-regression analysis were used to compare overall survival (OS) between patients treated with radical RT and radical CRT., Results: There were 83 patients over 65 years treated with either RT (n=21) or CRT (n=62). There was no significant difference in median OS between CRT versus RT (26.8 months vs 28.5 months, p=0.92). All patients receiving RT completed their treatment whereas 11% of CRT patients did not complete treatment., Conclusion: Survival in this non-trial older patient group managed with CRT is comparable to that reported in previous trials. RT shows better than expected outcomes which may reflect developments in RT technique. This review supports RT as an alternative in older patients, unfit for concurrent treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Target volumes for irradiation remain ill-defined for squamous cell cancer of unknown primary in the head and neck (SCCUP). The aim of this study was to compare involved neck only (INO) radiotherapy (RT) with irradiating involved neck plus potential mucosal primary sites and contralateral neck (MUC) in patients diagnosed and treated with modern diagnostics and techniques., Design: This is a retrospective cohort study. Patients with a diagnosis of SCCUP with unilateral neck disease were included., Results: Thirty patients were identified. All underwent FDG PET-CT. 47% of patients had HPV-positive SCC. 20 patients received RT to INO, 10 patients to MUC, all with volumetric modulated arc therapy (VMAT). A significantly lower dose for each organ at risk was delivered in INO-treated patients, with mean dose to contralateral parotid gland 57% less. The proportion of patients with late grade 2 or worse xerostomia was higher in MUC patients. The incidence of grade 2-3 mucositis (89% vs 45%) and grade 3 or worse dysphagia (50% vs 10%) was higher in MUC patients. Median follow-up was 31 months. No mucosal primaries emerged. Progression-free survival at 2 years was 74.7% for INO patients, 70% in the MUC group. Overall survival at 2 years was 79.7% in the INO group and 70% in the MUC patients., Conclusion: INO radiotherapy for patients with SCCUP of the head and neck is a safe treatment strategy resulting in clinically significant lower RT doses to OARS. Acute and late toxicities are reduced without detriment to patient survival., (© 2020 John Wiley & Sons Ltd.)