• 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.
    • Correction to: the impact of COVID-19 on interventional radiology services in the UK

      Zhong, J.; Datta, Anubhav; Gordon, T.; Adams, S.; Guo, T.; Abdelaziz, M.; Barbour, F.; Palkhi, E.; Adusumilli, P.; Oomerjee, M.; et al. (2021)
    • Correction to: Infantile fibrosarcoma with TPN3-NTRK3 fusion in a boy with Bloom Syndrome

      Huson, S. M.; Staab, T.; Pereira, M.; Ward, H.; Paredes, R.; Evans, D. G.; Baumhoer, D.; O'Sullivan, J.; Cheesman, E.; Schindler, D.; et al. (2021)
    • A phase II study of biodegradable stents plus palliative radiotherapy in oesophageal cancer

      Maishman, T.; Sheikh, Hamid Y; Boger, P.; Kelly, J.; Cozens, K.; Bateman, A.; Davies, S.; Fay, M.; Sharland, D.; Jackson, A.; et al. (2021)
      Aims: Self-expanding metal stents provide rapid improvement of dysphagia in oesophageal cancer but are associated with complications. The aim of the present study was to test the effectiveness of an alternative treatment of combining biodegradable stents with radiotherapy. Materials and methods: A Simon two-stage single-arm prospective phase II trial design was used to determine the efficacy of biodegradable stents plus radiotherapy in patients with dysphagia caused by oesophagus cancer who were unsuitable for radical treatment. Fourteen patients were recruited and data from 12 were included in the final analyses. Results: Five of 12 patients met the primary end point: one stent-related patient death; four further interventions for dysphagia within 16 weeks of stenting (41.7%, 95% confidence interval 15.2-72.3%). The median time to a 10-point deterioration of quality of life was 2.7 weeks. Nine patients died within 52 weeks of registration. The median time to death from any cause was 15.0 weeks (95% confidence interval 9.6-not reached). Conclusion: The high re-intervention observed, which met the pre-defined early stopping criteria, meant that the suggested alternative treatment was not sufficiently effective to be considered for a larger scale trial design. Further work is needed to define the place of biodegradable stents in the management of malignant oesophageal strictures.
    • 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.
    • Dataset for the reporting of carcinoma of the bladder-cystectomy, cystoprostatectomy and diverticulectomy specimens: recommendations from the International Collaboration on Cancer Reporting (ICCR)

      Comperat, E; Srigley, JR; Brimo, F; Delahunt, B; Koch, M; Lopez-Beltran, A; Reuter, V; Samaratunga, H; Shanks, Jonathan H; Tsuzuki, T; et al. (2020)
      The International Collaboration on Cancer Reporting (ICCR) is a not for profit organisation whose goal is to produce standardised internationally agreed and evidence-based datasets for pathology reporting. With input from pathologists worldwide, the datasets are intended to be uniform and structured. They include all items necessary for an objective and accurate pathology report which enables clinicians to apply the best treatment for the patient. This dataset has had input from a multidisciplinary ICCR expert panel. The rationale for some items being required and others recommended is explained, based on the latest literature. The dataset incorporates data from the World Health Organization (WHO) 2016, and also from the latest (8th edition) TNM staging system of the American Joint Committee on Cancer (AJCC). Fifteen required elements and eight recommended items are described. This dataset provides all the details for a precise and valuable pathology report required for patient management and prognostication. This dataset is intended for worldwide use, and should facilitate the collection of standardised comparable data on bladder carcinoma at an international level.
    • Two case reports involving therapeutic monoclonal anti-CD47 (Hu5F9-G4), it's effect on compatibility testing and subsequent selection of components for transfusion

      Reyland, L; Dwight, M; Bullock, T; Latham, T; Lord, K; Wardle, A; Palmer, D; Eggington, J; Callaghan, T; Seals, Deborah; et al. (2020)
    • Patient-reported functional outcomes after hypofractionated or conventionally fractionated radiation for prostate cancer: a national cohort study in England

      Nossiter, J; Sujenthiran, A; Cowling, TE; Parry, MG; Charman, SC; Cathcart, P; Clarke, Noel W; Payne, H; van der Meulen, J; Aggarwal, A; et al. (2020)
      PURPOSE: The aim of the current study was to determine patient-reported functional outcomes in men with prostate cancer (PCa) undergoing moderately hypofractionated (H-RT) or conventionally fractionated radiation therapy (C-RT) in a national cohort study. PATIENDS AND METHODS: All men diagnosed with PCa between April 2014 and September 2016 in the English National Health Service undergoing C-RT or H-RT were identified in the National Prostate Cancer Audit and mailed a questionnaire at least 18 months after diagnosis. We estimated differences in patient-reported urinary, bowel, sexual, and hormonal function-Expanded Prostate Cancer Index Composite short-form 26 domain scores on a 0 to 100 scale-and health-related quality of life-EQ-5D-5L on a 0 to 1 scale-using linear regression with adjustment for patient, tumor, and treatment-related factors in addition to GI and genitourinary baseline function, with higher scores representing better outcomes. RESULTS: Of the 17,058 men in the cohort, 77% responded: 8,432 men received C-RT (64.2%) and 4,699 H-RT (35.8%). Men in the H-RT group were older (age ³ 70 years: 67.5% v 60.9%), fewer men had locally advanced disease (56.5% v 71.3%), were less likely to receive androgen-deprivation therapy (79.5% v 87.8%), and slightly more men had pretreatment genitourinary procedures (24.2% v 21.2%). H-RT was associated with small increases in adjusted mean Expanded Prostate Cancer Index Composite short-form 26 sexual (3.3 points; 95% CI, 2.1 to 4.5; P < .001) and hormonal function scores (3.2 points; 95% CI, 1.8 to 4.6; P < .001). These differences failed to meet established thresholds for a clinically meaningful change. There were no statistically significant differences in urinary or bowel function and quality of life. CONCLUSION: This is the first national cohort study comparing functional outcomes after H-RT and C-RT reported by patients. These real-world results further support the use of H-RT as the standard for radiation therapy in men with nonmetastatic PCa.
    • Retrospective analyses of registry data for technical radiation oncology questions: apples versus pears or solid evidence?

      Nestle, U; Adebahr, S; van Herk, Marcel; Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; (2020)