• Introducing magnetic resonance imaging into the lung cancer radiotherapy workflow e An assessment of patient experience

      Bellhouse, Sarah; Brown, S; Dubec, Michael; Taylor, Sally; Hales, Rosie; Whiteside, Lee; Yorke, Janelle; Faivre-Finn, Corinne; Christie Patient Centred Research (CPCR), The Christie NHS Foundation Trust, UK (2021)
      Introduction: Magnetic resonance imaging (MRI) offers superior soft tissue contrast to computed tomography (CT), the current standard imaging modality for planning radiotherapy treatment. Improved soft tissue contrast could reduce uncertainties in identifying tumour and surrounding healthy tissues, potentially leading to improved outcomes in patients with lung cancer. This study explored patient experience of MR treatment planning scans in addition to a CT scan. Methods: Participants were recruited to the 'Magnetic Resonance Imaging for the Delineation of Organs At Risk and Target Volumes in Lung Cancer Patients (MR-Lung)' study at a UK specialist cancer centre. Participants completed their standard of care radiotherapy planning CT scan and two additional MRI scans. Baseline and post-scan questionnaires were completed assessing anxiety and claustrophobia. Motion artefact during MRI was assessed by a modified visual grading analysis. Sixteen participants completed semi-structured interviews; transcripts were analysed thematically. Results: 29 people (66% female; aged 54e89 years) participated. Nineteen participants completed all imaging and 10 participants withdrew before completion. There was minimal adverse impact on state and scan-specific anxiety levels from completing the MRI scans. Completers experienced significantly less scan-specific anxiety during MRI 1 compared to non-completers (U ¼ 33, z ¼ 1.98, p < 0.05). 78% of those who withdrew during or post MRI 1 were positioned 'arms up'. Motion artefact negatively impacted image quality in 34% of scans. Participants commonly reported concerns during MRI; noise, claustrophobia and pain in upper limbs. Conclusion: Two thirds of participants tolerated two additional MR scans with minimal adverse impact on anxiety levels.
    • Determining the parameter space for effective oxygen depletion for FLASH radiation therapy

      Rothwell, Bethany C; Kirkby, Norman; Merchant, Michael J; Chadwick, Amy; Lowe, Matthew; Mackay, Ranald I; Hendry, Jolyon H|Kirkby, Karen J; Division of Cancer Sciences, The University of Manchester Faculty of Biology Medicine and Health, Manchester (2021)
      There has been a recent revival of interest in the FLASH effect, after experiments have shown normal tissue sparing capabilities of ultra-high-dose-rate radiation with no compromise on tumour growth restraint. A model has been developed to investigate the relative importance of a number of fundamental parameters considered to be involved in the oxygen depletion paradigm of induced radioresistance. An example eight-dimensional parameter space demonstrates the conditions under which radiation may induce sufficient depletion of oxygen for a diffusion-limited hypoxic cellular response. Initial results support experimental evidence that FLASH sparing is only achieved for dose rates on the order of tens of Gy/s or higher, for a sufficiently high dose, and only for tissue that is slightly hypoxic at the time of radiation. We show that the FLASH effect is the result of a number of biological, radiochemical and delivery parameters. Also, the threshold dose for a FLASH effect occurring would be more prominent when the parameterisation was optimised to produce the maximum effect. The model provides a framework for further FLASH-related investigation and experimental design. An understanding of the mechanistic interactions producing an optimised FLASH effect is essential for its translation into clinical practice.
    • Bariatric surgery leads to an improvement in small nerve fibre damage in subjects with obesity

      Azmi, S.; Ferdousi, M.; Liu, Y.; Adam, Safwaan; Iqbal, Z.; Dhage, Shaishav; Ponirakis, G.; Siahmansur, T.; Marshall, A.; Petropoulos, I.; et al. (2021)
      Introduction: Subjects with obesity have metabolic risk factors for nerve fibre damage. Because bariatric surgery improves these risk factors we have assessed whether this can ameliorate nerve fibre damage. Methods: Twenty-six obese subjects without diabetes (age: 46.23 ± 8.6, BMI: 48.7 ± 1.5, HbA1c: 38.0 ± 4.5) and 20 controls (age: 48.3 ± 6.2, BMI: 26.8 ± 4.2, HbA1c: 39.1 ± 2.6) underwent detailed assessment of neuropathy at baseline and 12 months after bariatric surgery. Results: Obese subjects had normal peroneal (45.9 ± 5.5 vs. 48.1 ± 4.5, P = 0.1) and sural (46.9 ± 7.6 vs. 47.9 ± 10.6, P = 0.1) nerve conduction velocity, but a significantly higher neuropathy symptom profile (NSP) (4.3 ± 5.7 vs. 0.3 ± 0.6, P = 0.001), vibration perception threshold (VPT) (V) (10.2 ± 6.8 vs. 4.8 ± 2.7, P < 0.0001), warm threshold (C°) (40.4 ± 3.5 vs. 37.2 ± 1.8, P = 0.003) and lower peroneal (3.8 ± 2.2 vs. 4.9 ± 2.2, P = 0.02) and sural (8.9 ± 5.8 vs. 15.2 ± 8.5, P < 0.0001) nerve amplitude, deep breathing-heart rate variability (DB-HRV) (beats/min) (21.7 ± 4.1 vs. 30.1 ± 14, P = 0.001), corneal nerve fibre density (CNFD) (n/mm2) (25.6 ± 5.3 vs. 32.0 ± 3.1, P < 0.0001), corneal nerve branch density (CNBD) (n/mm2) (56.9 ± 27.5 vs. 111.4 ± 30.7, P < 0.0001) and corneal nerve fibre length (CNFL) (mm/mm2) (17.9 ± 4.1 vs. 29.8 ± 4.9, P < 0.0001) compared to controls at baseline. In control subjects there was no change in neuropathy measures over 12 months. However, 12 months after bariatric surgery there was a significant reduction in BMI (33.7 ± 1.7 vs. 48.7 ± 1.5, P = 0.001), HbA1c (34.3 ± 0.6 vs. 38.0 ± 4.5, P = 0.0002), triglycerides (mmol/l) (1.3 ± 0.6 vs. 1.6 ± 0.8, P = 0.005) and low-density lipoprotein cholesterol (mmol/l) (2.7 ± 0.7 vs. 3.1 ± 0.9, P = 0.02) and an increase in high-density lipoprotein cholesterol (mmol/l) (1.2 ± 0.3 vs. 1.04 ± 0.2, P = 0.002). There was a significant improvement in NSP (1.6 ± 2.7 vs. 4.3 ± 5.7, P = 0.004), neuropathy disability score (0.3 ± 0.9 vs. 1.3 ± 2.0, P = 0.03), CNFD (28.2 ± 4.4 vs. 25.6 ± 5.3, P = 0.03), CNBD (64.7 ± 26.1 vs. 56.9 ± 27.5, P = 0.04) and CNFL (20.4 ± 1.2 vs. 17.9 ± 4.1, P = 0.02), but no change in cold and warm threshold, VPT, DB-HRV or nerve conduction velocity and amplitude. Increase in CNFD correlated with a decrease in triglycerides (r = -0.45, P = 0.04). Conclusion: Obese subjects have evidence of neuropathy, and bariatric surgery leads to an improvement in weight, HbA1c, lipids, neuropathic symptoms and deficits and small nerve fibre regeneration without a change in quantitative sensory testing, autonomic function or neurophysiology.
    • Pembrolizumab plus ipilimumab or placebo for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score ≥ 50%: randomized, double-blind phase III KEYNOTE-598 study

      Boyer, M.; Şendur, M. A. N.; Rodríguez-Abreu, D.; Park, K.; Lee, D. H.; Çiçin, I.; Yumuk, P. F.; Orlandi, F. J.; Leal, T. A.; Molinier, O.; et al. (2021)
      Purpose: Pembrolizumab monotherapy is standard first-line therapy for metastatic non-small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 50% without actionable driver mutations. It is not known whether adding ipilimumab to pembrolizumab improves efficacy over pembrolizumab alone in this population. Methods: In the randomized, double-blind, phase III KEYNOTE-598 trial (ClinicalTrials.gov identifier: NCT03302234), eligible patients with previously untreated metastatic NSCLC with PD-L1 TPS ≥ 50% and no sensitizing EGFR or ALK aberrations were randomly allocated 1:1 to ipilimumab 1 mg/kg or placebo every 6 weeks for up to 18 doses; all participants received pembrolizumab 200 mg every 3 weeks for up to 35 doses. Primary end points were overall survival and progression-free survival. Results: Of the 568 participants, 284 were randomly allocated to each group. Median overall survival was 21.4 months for pembrolizumab-ipilimumab versus 21.9 months for pembrolizumab-placebo (hazard ratio, 1.08; 95% CI, 0.85 to 1.37; P = .74). Median progression-free survival was 8.2 months for pembrolizumab-ipilimumab versus 8.4 months for pembrolizumab-placebo (hazard ratio, 1.06; 95% CI, 0.86 to 1.30; P = .72). Grade 3-5 adverse events occurred in 62.4% of pembrolizumab-ipilimumab recipients versus 50.2% of pembrolizumab-placebo recipients and led to death in 13.1% versus 7.5%. The external data and safety monitoring committee recommended that the study be stopped for futility and that participants discontinue ipilimumab and placebo. Conclusion: Adding ipilimumab to pembrolizumab does not improve efficacy and is associated with greater toxicity than pembrolizumab monotherapy as first-line treatment for metastatic NSCLC with PD-L1 TPS ≥ 50% and no targetable EGFR or ALK aberrations. These data do not support use of pembrolizumab-ipilimumab in place of pembrolizumab monotherapy in this population.
    • Haematological malignancy and nosocomial transmission are associated with an increased risk of death from COVID-19: results of a multi-center UK cohort

      Bhogal, T.; Khan, U. T.; Lee, Rebecca; Stockdale, A.; Hesford, C.; Potti-Dhananjaya, V.; Jathanna, A.; Rahman, S.; Tivey, Ann; Shotton, Rohan; et al. (2021)
      The COVID-19 pandemic has been a disruptive event for cancer patients, especially those with haematological malignancies (HM). They may experience a more severe clinical course due to impaired immune responses. This multi-center retrospective UK audit identified cancer patients who had SARS-CoV-2 infection between 1 March and 10 June 2020 and collected data pertaining to cancer history, COVID-19 presentation and outcomes. In total, 179 patients were identified with a median age of 72 (IQR 61, 81) and follow-up of 44 days (IQR 42, 45). Forty-one percent were female and the overall mortality was 37%. Twenty-nine percent had HM and of these, those treated with chemotherapy in the preceding 28 days to COVID-19 diagnosis had worse outcome compared with solid malignancy (SM): 62% versus 19% died [HR 8.33 (95% CI, 2.56-25), p < 0.001]. Definite or probable nosocomial SARS-CoV-2 transmission accounted for 16% of cases and was associated with increased risk of death (HR 2.47, 95% CI 1.43-4.29, p = 0.001). Patients with haematological malignancies and those who acquire nosocomial transmission are at increased risk of death. Therefore, there is an urgent need to reassess shielding advice, reinforce stringent infection control, and ensure regular patient and staff testing to prevent nosocomial transmission.
    • ALK-negative anaplastic large cell lymphoma: features and outcomes of 235 patients from the International T-Cell Project

      Shustov, A.; Cabrera, M. E.; Civallero, M.; Bellei, M.; Ko, Y. H.; Manni, M.; Skrypets, T.; Horwitz, S. M.; De Souza, C. A.; Radford, John A; et al. (2021)
      Anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALK- ALCL) is an aggressive neoplasm of T-cell/null-cell lineage. The T-Cell Project is a global prospective cohort study that consecutively enrolled patients newly diagnosed with peripheral T-cell lymphoma, registered through a centralized computer database between September 2006 and February 2018. Of 1553 validated cases from 74 sites in 13 countries worldwide, 235 were reported as ALK- ALCL. The median age at diagnosis was 54 years (range, 18-89 years), with a male predominance (62%). Stage III to IV disease was identified in 71% of patients, bulky disease and bone marrow involvement were uncommon, and 66% of patients presented with a low (0-1) International Prognostic Index score. Of all treated patients, 85% received multiagent initial chemotherapy, and 8% were consolidated with autologous hematopoietic cell transplantation. The initial overall and complete response rates were 77% and 63%, respectively. After a median follow-up of 52 months (95% confidence interval [CI], 41-63), the median progression-free survival (PFS) and overall survival (OS) were 41 months (95% CI, 17-62) and 55 months (95% CI, 36-75), respectively. The 3- and 5-year PFS rates were 52% and 43%, and the 3- and 5-year OS rates were 60% and 49%. Treatments containing both anthracycline and etoposide were associated with superior OS (P = .05) but not PFS (P = .18). In this large prospective cohort study, outcomes comparable to those previously reported in the retrospective International Peripheral T-Cell Lymphoma Project were observed. The study underscores the need for introducing novel platforms for ALK- ALCL and establishes a benchmark for future clinical trials.
    • IPEM topical report: guidance on the use of MRI for external beam radiotherapy treatment planning

      Speight, R.; Dubec, Michael; Eccles, Cynthia L; George, B.; Henry, A.; Herbert, T.; Johnstone, R.; Liney, G. P.; McCallum, H. M.; Schmidt, M. A.; et al. (2021)
      This document gives guidance for multidisciplinary teams within institutions setting up and using an MRI-guided radiotherapy (RT) treatment planning service. It has been written by a multidisciplinary working group from the Institute of Physics and Engineering in Medicine (IPEM). Guidance has come from the experience of the institutions represented in the IPEM working group, in consultation with other institutions, as well as information taken from the literature. Guidance is only given for MRI acquired for external beam RT treatment planning in a CT-based workflow, i.e. when MRI is acquired and registered to CT with the purpose of aiding delineation of target or organ at risk volumes. MRI-only RT and other RT treatment types such as brachytherapy and gamma radiosurgery are not considered in scope here, although some of the major themes discussed are relevant. The aim was to produce guidance that will be useful for institutions who are setting up and using a dedicated MR scanner for RT (referred to as an MR-sim) and those who will have limited time on an MR scanner potentially managed outside of the RT department, often by radiology. Although not specifically covered in this document, there is an increase in the use of hybrid MRI-linac systems worldwide and brief comments are included to highlight any crossover with the early implementation of this technology. In this document, advice is given on introducing an RT workload onto a non-RT-dedicated MR scanner, as well as planning for installation of an MR scanner dedicated for RT. Next, practical guidance is given on the following, in the context of RT planning: training and education for all staff working in and around an MR scanner; RT patient set-up on an MR scanner; MRI sequence optimisation for RT purposes; commissioning and quality assurance (QA) to be performed on an MR scanner; and MRI to CT registration, including commissioning and QA.
    • Treatment of infections in cancer patients: an update from the neutropenia, infection and myelosuppression study group of the Multinational Association for Supportive Care in Cancer (MASCC)

      Rapoport, B. L.; Cooksley, Timothy J; Johnson, D. B.; Anderson, R.; Shannon, V. R.; Department of Immunology, Faculty of Health Sciences, University of Pretoria , Pretoria, South Africa. (2021)
      Introduction: Patients with hematological and advanced solid malignancies have acquired immune dysfunction, often exacerbated by treatment, posing a significant risk for development of infections. This review evaluates the utility of current clinical and treatment guidelines, in the setting of management of infections in cancer patients. Areas covered: : These include causes of infection in cancer patients, management of patients with high-risk and low-risk febrile neutropenia, management of low-risk patients in an outpatient setting, the role of granulocyte colony-stimulating factor (G-CSF) in the prevention and treatment of neutropenia-related infections, management of lung infections in various clinical settings, and emerging challenges surrounding the risk of infection in cancer patients treated with novel treatments. The literature search was performed by accessing PubMed and other databases, focusing on published clinical trials of relevant anti-cancer agents and diseases, primarily covering the recent past, but also including several key studies published during the last decade and, somewhat earlier in a few cases. Expert review: Notwithstanding the promise of gene therapy/gene editing in hematological malignancies and some types of solid cancers, innovations introduced in clinical practice include more discerning clinical management such as the generalized use of biosimilar formulations G-CSF and the implementation of novel, innovative immunotherapies.
    • Small-cell lung cancer

      Rudin, C. M.; Brambilla, E.; Faivre-Finn, Corinne; Sage, J.; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA (2021)
      Small-cell lung cancer (SCLC) represents about 15% of all lung cancers and is marked by an exceptionally high proliferative rate, strong predilection for early metastasis and poor prognosis. SCLC is strongly associated with exposure to tobacco carcinogens. Most patients have metastatic disease at diagnosis, with only one-third having earlier-stage disease that is amenable to potentially curative multimodality therapy. Genomic profiling of SCLC reveals extensive chromosomal rearrangements and a high mutation burden, almost always including functional inactivation of the tumour suppressor genes TP53 and RB1. Analyses of both human SCLC and murine models have defined subtypes of disease based on the relative expression of dominant transcriptional regulators and have also revealed substantial intratumoural heterogeneity. Aspects of this heterogeneity have been implicated in tumour evolution, metastasis and acquired therapeutic resistance. Although clinical progress in SCLC treatment has been notoriously slow, a better understanding of the biology of disease has uncovered novel vulnerabilities that might be amenable to targeted therapeutic approaches. The recent introduction of immune checkpoint blockade into the treatment of patients with SCLC is offering new hope, with a small subset of patients deriving prolonged benefit. Strategies to direct targeted therapies to those patients who are most likely to respond and to extend the durable benefit of effective antitumour immunity to a greater fraction of patients are urgently needed and are now being actively explored.
    • Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer

      Karunamuni, R. A.; Huynh-Le, M. P.; Fan, C. C.; Thompson, W.; Eeles, R. A.; Kote-Jarai, Z.; Muir, K.; Lophatananon, A.; Schleutker, J.; Pashayan, N.; et al. (2021)
      Background: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46). Materials and method: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy. Results: 166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer. Conclusions: Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.
    • A soft silicone foam dressing that aids healing and comfort in oncology care

      Pramod, Susy; Tissue Viability Nurse, The Christie NHS Foundation Trust, Manchester. (2021)
      Maintaining skin integrity plays a key role in the ongoing care and comfort of patients at the end of life. Unfortunately, patients receiving cancer treatments are at higher risk of altered skin integrity. Cancer treatments involve multiple modalities, all of which impair wound healing. Excess exudate can be distressing to patients, resulting in catastrophic damage to the wound bed and surrounding skin, reducing quality of life and increasing the need for specialist services. This article describes the use of the Kliniderm foam silicone range of dressings, in combination with best practice, in the treatment of wounds in the oncology setting. The case study evidence presented indicates that this range of dressings is useful in the management of radiotherapy and oncology wounds. It had a positive effect on the exudate level, wound-association pain and the peri-wound skin in these patients, aiding the management of the wound bed.
    • Preventing and managing device-related pressure ulcers in oncology

      Pramod, Susy; Tissue Viability Nurse, The Christie NHS Foundation Trust, Manchester, UK. (2021)
      There is growing evidence that medical device-related pressure ulcers (MDRPUs) are an increasing healthcare concern in all aspects of care. It is especially important to develop an individualised care plan for people at the end of life to prevent pressure ulceration and to treat this if it occurs. Tissue viability nurses have a responsibility to review and assess new prophylactic devices and dressings, to ensure a high standard of care is provided. This article describes the use of a soft silicone dressing, Kliniderm foam silicone lite, in combination with best practice, to prevent MDRPUs in the oncology setting. Three case studies show that the dressing helped avoid the occurrence of ulceration on the ears and nose in patients receiving oxygen through a nasal cannula.
    • Circulating tumour DNA as a biomarker in resectable and irresectable stage IV colorectal cancer; a systematic review and meta-analysis

      Jones, R. P.; Pugh, S. A.; Graham, J.; Primrose, J. N.; Barriuso, Jorge; School of Cancer Studies, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Department of Hepatobiliary Surgery, Liverpool University Teaching Hospitals NHS Foundation Trust, Liverpool, UK. (2021)
      Background: For patients with metastatic colorectal cancer, stratification for treatment (surgery or chemotherapy) is often based on crude clinicopathological characteristics like tumour size and number of lesions. Circulating tumour DNA (ctDNA) acts as a potential biomarker of disease trajectory and biology, allowing better stratification. This study aims to systematically review ctDNA in stage IV colorectal cancer to assess its potential role as a prospective biomarker to guide management decisions. Methods: A literature search was performed to identify studies where the measurement of ctDNA in stage IV colorectal cancer was correlated with a clinical outcome (radiological response, secondary resection rate, PFS, DFS or OS). Results: Twenty-eight studies were included, reporting on 2823 patients. Circulating tumour DNA was detectable in between 80% and 90% of patients prior to treatment. Meta-analysis identified a strong correlation between detectable ctDNA after treatment (surgery or chemotherapy) and overall survival (HR 2.2, 95% CI 1.79-2.69, p < 0.00001), as well as progression-free survival (HR 3.15, 95% CI 2.10-4.73, p < 0.00001). ctDNA consistently offered an early marker of long-term prognosis in irresectable disease, with changes after one cycle of systemic therapy demonstrating prognostic value. In resectable disease treated with curative intent, detection of ctDNA offered a lead time over radiological recurrence of 10 months. Conclusion: Circulating tumour DNA is detectable in the majority of resectable and irresectable patients. The presence of ctDNA is clearly associated with shorter overall survival, with changes in ctDNA an early biomarker of adverse disease behaviour. Prospective trials are essential to test its clinical efficacy.
    • Stereotactic ablative body radiotherapy in patients with oligometastatic cancers: a prospective, registry-based, single-arm, observational, evaluation study

      Chalkidou, A.; Macmillan, T.; Grzeda, M. T.; Peacock, J.; Summers, J.; Eddy, S.; Coker, B.; Patrick, H.; Powell, H.; Berry, L.; et al. (2021)
      Background: Stereotactic ablative body radiotherapy (SABR) is increasingly being used to treat oligometastatic cancers, but high-level evidence to provide a basis for policy making is scarce. Additional evidence from a real-world setting is required. We present the results of a national study of patients with extracranial oligometastases undergoing SABR, representing the largest dataset, to our knowledge, on outcomes in this population so far. Methods: In 2015, National Health Service (NHS) England launched a Commissioning through Evaluation scheme that funded a prospective, registry-based, single-arm, observational, evaluation study of patients with solid cancer and extracranial oligometastases treated with SABR. Prescribed doses ranged from 24-60 Gy administered in three to eight fractions. The study was done at 17 NHS radiotherapy centres in England. Patients were eligible for the scheme if aged 18 years or older with confirmed primary carcinoma (excluding haematological malignancies), one to three extracranial metastatic lesions, a disease-free interval from primary tumour development to metastases of longer than 6 months (with the exception of synchronous colorectal liver metastases), a WHO performance status of 2 or lower, and a life expectancy of at least 6 months. The primary outcome was overall survival at 1 year and 2 years from the start of SABR treatment. The study is now completed. Findings: Between June 15, 2015, and Jan 30, 2019, 1422 patients were recruited from 17 hospitals in England. The median age of the patients was 69 years (IQR 62-76), and the most common primary tumour was prostate cancer (406 [28·6%] patients). Median follow-up was 13 months (IQR 6-23). Overall survival was 92·3% (95% CI 90·5-93·9) at 1 year and 79·2% (76·0-82·1) at 2 years. The most common grade 3 adverse event was fatigue (28 [2·0%] of 1422 patients) and the most common serious (grade 4) event was increased liver enzymes (nine [0·6%]). Notreatment-related deaths were reported. Interpretation: In patients with extracranial oligometastatic cancer, use of SABR was associated with high overall survival and low toxicity. 'The study findings complement existing evidence from a randomised, phase 2 trial, and represent high-level, real-world evidence supporting the use of SABR in this patient cohort, with a phase 3 randomised, controlled trial to confirm these findings underway. Based on the selection criteria in this study, SABR was commissioned by NHS England in March, 2020, as a treatment option for patients with oligometastatic disease.
    • Management of penile cancer patients during the COVID-19 pandemic: An eUROGEN accelerated Delphi consensus study

      Cakir, O. O.; Castiglione, F.; Tandogdu, Z.; Collins, J.; Alnajjar, H. M.; Akers, C.; Albersen, M.; Alifrangis, C.; Ayres, B.; Brouwer, O.; et al. (2021)
      Objectives: To develop an international consensus on managing penile cancer patients during the COVID-19 acute waves. A major concern for patients with penile cancer during the coronavirus disease 2019 (COVID-19) pandemic is how the enforced safety measures will affect their disease management. Delays in diagnosis and treatment initiation may have an impact on the extent of the primary lesion as well as the cancer-specific survival because of the development and progression of inguinal lymph node metastases. Materials and methods: A review of the COVID-19 literature was conducted in conjunction with analysis of current international guidelines on the management of penile cancer. Results were presented to an international panel of experts on penile cancer and infection control by a virtual accelerated Delphi process using 4 survey rounds. Consensus opinion was defined as an agreement of ≥80%, which was used to reconfigure management pathways for penile cancer. Results: Limited evidence is available for delaying penile cancer management. The consensus rate of agreement was 100% that penile cancer pathways should be reconfigured, and measures should be developed to prevent perioperative nosocomial transmission of COVID-19. The panel also reached a consensus on several statements aimed at reconfiguring the management of penile cancer patients during the COVID-19 pandemic. Conclusions: The international consensus panel proposed a framework for the diagnostic and invasive therapeutic procedures for penile cancer within a low-risk environment for COVID-19
    • Prospects for personalised treatment of patients with radioiodine-avid locally recurrent or metastatic thyroid cancer

      Beasley, M.; Garcez, Kate; Bristol Cancer Institute, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, (2021)
      Although most patients with metastatic or inoperable locally recurrent differentiated thyroid cancer have radioiodine-avid disease, the outcome for patients who do not achieve remission with radioiodine therapy is poor. Most centres use fixed empirical activities of radioiodine to treat these patients, which is in contrast to other areas of oncology, where there is a shift to more individualised treatment. The use of dosimetry techniques to calculate a more appropriate activity of radioiodine for each patient may increase the effectiveness of radioiodine therapy but is more complex, time-consuming and of unproven benefit. This review addresses some of the limitations of empirical radioiodine therapy, discusses existing dosimetry-based approaches to individualising therapy and proposes further work in this area. A prospective randomised controlled trial comparing empirical activities of radioiodine with activities guided by a combination of lesional dosimetry and maximum safe dose has not been carried out previously. Although considerable challenges in the design of such a study remain, a network of centres in the UK now has the potential to take this forward.
    • Intensity-modulated radiotherapy for rectal cancer in the UK in 2020

      Hanna, C. R.; Slevin, F.; Appelt, A.; Beavon, M.; Adams, R.; Arthur, Claire; Beasley, M.; Duffton, A.; Gilbert, A.; Gollins, S.; et al. (2021)
      Aims: Preoperative (chemo)radiotherapy followed by total mesorectal excision is the current standard of care for patients with locally advanced rectal cancer. The use of intensity-modulated radiotherapy (IMRT) for rectal cancer is increasing in the UK. However, the extent of IMRT implementation and current practice was not previously known. A national survey was commissioned to investigate the landscape of IMRT use for rectal cancer and to inform the development of national rectal cancer IMRT guidance. Materials and methods: A web-based survey was developed by the National Rectal Cancer IMRT Guidance working group in collaboration with the Royal College of Radiologists and disseminated to all UK radiotherapy centres. The survey enquired about the implementation of IMRT with a focus on the following aspects of the workflow: dose fractionation schedules and use of a boost; pre-treatment preparation and simulation; target volume/organ at risk definition; treatment planning and treatment verification. A descriptive statistical analysis was carried out. Results: In total, 44 of 63 centres (70%) responded to the survey; 30/44 (68%) and 36/44 (82%) centres currently use IMRT to treat all patients and selected patients with rectal cancer, respectively. There was general agreement concerning several aspects of the IMRT workflow, including patient positioning, use of intravenous contrast and bladder protocols. Greater variation in practice was identified regarding rectal protocols; use of a boost to primary/nodal disease; target volume delineation; organ at risk delineation and dose constraints and treatment verification. Delineation of individual small bowel loops and daily volumetric treatment verification were considered potentially feasible by most centres. Conclusion: This survey identified that IMRT is already used to treat rectal cancer in many UK radiotherapy centres, but there is heterogeneity between centres in its implementation and practice. These results have been a valuable aid in framing the recommendations within the new National Rectal Cancer IMRT Guidance.
    • Ultraviolet radiation drives mutations in a subset of mucosal melanomas

      Mundra, Piyushkumar A; Dhomen, Nathalie; Rodrigues, M.; Mikkelsen, L. H.; Cassoux, N.; Brooks, Kelly; Valpione, Sara; Reis-Filho, J. S.; Heegaard, S.; Stern, M. H.; et al. (2021)
      Although identified as the key environmental driver of common cutaneous melanoma, the role of ultraviolet radiation (UVR)-induced DNA damage in mucosal melanoma is poorly defined. We analyze 10 mucosal melanomas of conjunctival origin by whole genome sequencing and our data shows a predominance of UVR-associated single base substitution signature 7 (SBS7) in the majority of the samples. Our data shows mucosal melanomas with SBS7 dominance have similar genomic patterns to cutaneous melanomas and therefore this subset should not be excluded from treatments currently used for common cutaneous melanoma.
    • Renal myopericytoma: A case report and literature review

      Riley, T.; Shenjere, Patrick; Jain, A.; Sunder, S.; North Manchester General Hospital, Pennine Acute NHS Hospitals Trust, Delaunay's Road, Manchester, M8 5RB (2021)
      Renal myopericytoma is an extremely rare entity with just 11 cases reported in the literature. We report the case of a 57 year old Caucasian man who was found to have a renal myopericytoma following nephrectomy for suspected renal cell carcinoma. Renal myopericytoma has a distinct morphological overlap with other pericytic tumours and significant histological variation has been noted between cases reported to date. Further characterising this novel tumour is vital to identify subtypes within this spectrum, understand its behaviour and to identify imaging trends which may lead to pre-operative diagnosis in order to potentially avoid radical treatment.