CCC publication: Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer

Citation: Journal of clinical oncology. 2020, 38(28), 3261-3272. Epub 2020 Jul 14.

Author: Brunt A.M.; Haviland J.S.; Sydenham M.; Bliss J.M.; Agrawal R.K.; Algurafi H.; Alhasso A.; Barrett-Lee P.; Passant H.; Bliss P.; Bloomfield D.; Tremlett J.; Bowen J.; Donovan E.; Goodman A.; Harnett A.; Hogg M.; Kumar S.; Quigley M.; Sherwin L.; Stewart A.; Syndikus I.; Tsang Y.; Venables K.; Wheatley D.; Yarnold J.R.

Abstract: Purpose: Previous studies of hypofractionated adjuvant whole-breast radiotherapy for early breast cancer established a 15- or 16-fraction (fr) regimen as standard. The FAST Trial (CRUKE/04/015) evaluated normal tissue effects (NTE) and disease outcomes after 5-fr regimens. Ten-year results are presented.

Methods: Women ≥ 50 years of age with low-risk invasive breast carcinoma (pT1-2 pN0) were randomly assigned to 50 Gy/25 fr (5 weeks) or 30 or 28.5 Gy in 5 once-weekly fr of 6.0 or 5.7 Gy. The primary end point was change in photographic breast appearance at 2 and 5 years; secondary end points were physician assessments of NTE and local tumor control. Odds ratios (ORs) from longitudinal analyses compared regimens.

Results: A total of 915 women were recruited from 18 UK centers (2004-2007). Five-year photographs were available for 615/862 (71%) eligible patients. ORs for change in photographic breast appearance were 1.64 (95% CI, 1.08 to 2.49; P = .019) for 30 Gy and 1.10 (95% CI, 0.70 to 1.71; P = .686) for 28.5 Gy versus 50 Gy. α/β estimate for photographic end point was 2.7 Gy (95% CI, 1.5 to 3.9 Gy), giving a 5-fr schedule of 28 Gy (95% CI, 26 to 30 Gy) estimated to be isoeffective with 50 Gy/25 fr. ORs for any moderate/marked physician-assessed breast NTE (shrinkage, induration, telangiectasia, edema) were 2.12 (95% CI, 1.55 to 2.89; P < .001) for 30 Gy and 1.22 (95% CI, 0.87 to 1.72; P = .248) for 28.5 Gy versus 50 Gy. With 9.9 years median follow-up, 11 ipsilateral breast cancer events (50 Gy: 3; 30 Gy: 4; 28.5 Gy: 4) and 96 deaths (50 Gy: 30; 30 Gy: 33; 28.5 Gy: 33) have occurred.

Conclusion: At 10 years, there was no significant difference in NTE rates after 28.5 Gy/5 fr compared with 50 Gy/25 fr, but NTE were higher after 30 Gy/5 fr. Results confirm the published 3-year findings that a once-weekly 5-fr schedule of whole-breast radiotherapy can be identified that appears to be radiobiologically comparable for NTE to a conventionally fractionated regimen.

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CCC publication: Interpreting clinical significance of machine learning approaches and radiomics in radiation oncology trials

Citation: Radiotherapy and Oncology. 2020, 152, 78-9

Author: Ian S. Boon, Moi H. Yap, Tracy P.T Au Yong, Cheng S. Boon,

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CCC publication: A mathematical model of dynamics of cell populations in squamous epithelium after irradiation

Citation: International Journal of Radiation Biology. 2020, 96(9), 1165-72. [epub 2020, July 17]

Author: Parga-Pazos M.; Lopez Pouso O.; Pardo-Montero J.; Fenwick J.D.
Abstract: PURPOSE: To develop multi-compartment mechanistic models of dynamics of stem and functional cell populations in epithelium after irradiation. Methods and materials: We present two models, with three (3C) and four (4C) compartments respectively. We use delay differential equations, and include accelerated proliferation, loss of division asymmetry, progressive death of abortive stem cells, and turnover of functional cells. The models are used to fit experimental data on the variations of the number of cells in mice mucosa after irradiation with 13 Gy and 20 Gy. Akaike information criteria (AIC) was used to evaluate the performance of each model. RESULTS: Both 3C and 4C models provide good fits to experimental data for 13 Gy. Fits for 20 Gy are slightly poorer and may be affected by larger uncertainties and fluctuations of experimental data. Best fits are obtained by imposing constraints on the fitting parameters, so to have values that are within experimental ranges. There is some degeneration in the fits, as different sets of parameters provide similarly good fits. CONCLUSIONS: The models provide good fits to experimental data. Mechanistic approaches like this can facilitate the development of mucositis response models to nonstandard schedules/treatment combinations not covered by datasets to which phenomenological models have been fitted. Studying the dynamics of cell populations in multifraction treatments, and finding links with induced toxicity, is the next step of this work.

CCC publication: Considerations for the treatment of pancreatic cancer during the COVID-19 pandemic: the UK consensus position

Citation: British Journal of Cancer. 2020, 123(5), 709-13 [Epub ahead of print]

Author: Jones C.M.; Goody R.; Radhakrishna G.; Valle J.W.; Aitken K.; Hunt A.; Bridgewater J.; Corrie P.; Eatock M.; Ghaneh P.; Good J.; Grose D.; Holyoake D.; Jamieson N.B.; Palmer D.H.; Soonawalla Z.; Hawkins M.A.; Mukherjee S. (somnath.mukherjee@oncology.ox.ac.uk)

Abstract: The coronavirus disease 2019 (COVID-19) pandemic epicentre has moved to the USA and Europe, where it is placing unprecedented demands on healthcare resources and staff availability. These service constraints, coupled with concerns relating to an increased incidence and severity of COVID-19 among patients with cancer, should lead to re-consideration of the risk–benefit balance for standard treatment pathways. This is of particular importance to pancreatic cancer, given that standard diagnostic modalities such as endoscopy may be restricted, and that disease biology precludes significant delays in treatment. In light of this, we sought consensus from UK clinicians with an interest in pancreatic cancer for management approaches that would minimise patient risk and accommodate for healthcare service restrictions. The outcomes are described here and include recommendations for treatment prioritisation, strategies to bridge to later surgical resection in resectable disease and factors that modify the risk–benefit balance for treatment in the resectable through to the metastatic settings. Priority is given to strategies that limit hospital visits, including through the use of hypofractionated precision radiotherapy and chemoradiotherapy treatment approaches.
Subject terms: Pancreatic cancer, Radiotherapy, Chemotherapy

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CCC publication: Liquid biopsy mutation panel for non-small cell lung cancer: analytical validation and clinical concordance

Citation: npj Precision Oncology. 2020, 4(1), 15

Author: Schwartzberg L.S. (lschwartzberg@westclinic.com); Horinouchi H.; Chan D.; Chernilo S.; Tsai M.L.; Isla D.; Escriu C.; Bennett J.P.; Clark-Langone K.; Svedman C.; Alexander G.; Baehner F.L.; Bergamaschi A.; Davison D.; Eberhard D.A.; Han J.; Lopatin M.; Tomasini P.; Bauer T.; Crown J.; Gabrail N.; Irvin W.; Orsini J.; Sumrall B.T.

Abstract: Molecular testing for genomic variants is recommended in advanced non-small cell lung cancer (NSCLC). Standard tissue biopsy is sometimes infeasible, procedurally risky, or insufficient in tumor tissue quantity. We present the analytical validation and concordance study of EGFR variants using a new 17-gene liquid biopsy assay (NCT02762877). Of 144 patients enrolled with newly diagnosed or progressive stage IV nonsquamous NSCLC, 140 (97%) had liquid assay results, and 117 (81%) had both EGFR blood and tissue results. Alterations were detected in 58% of liquid samples. Overall tissue-liquid concordance for EGFR alterations was 94.0% (95% CI 88.1%, 97.6%) with positive percent agreement of 76.7% (57.7%, 90.1%) and negative percent agreement of 100% (95.8%, 100%). Concordance for ALK structural variants was 95.7% (90.1%, 98.6%). This assay detected alterations in other therapeutically relevant genes at a rate similar to tissue analysis. These results demonstrate the analytical and clinical validity of this 17-gene assay.
Subject terms: Cancer genomics, Cancer genomics

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CCC publication: Weekly platinum-based chemotherapy versus 3-weekly platinum-based chemotherapy for newly diagnosed ovarian cancer (ICON8): quality-of-life results of a phase 3, randomised, controlled trial

Citation: The Lancet. Oncology. 2020, 21(7), 969–77

Author: C. Lucy Dalton, Kristijonas Milinis, David Houghton, Paul Ridley, Katharine Davies, Richard Williams, David Hamilton, Mark D. Wilkie, Anne Markey, Kim Clarke, Matthew Lofthouse, Timothy R. Helliwell, Asterios Triantafyllou, Jennifer Rodrigues, Krishna Bheemireddy, Ged Dempsey, Rebecca Hanlon, Hulya Wieshmann, Anoop Haridass, Caroline Brammer, David Husband, Aditya Shenoy, Christopher Loh, Nicholas J. Roland, Fazilet Bekiroglu, Sankalap Tandon, Jeffrey Lancaster, Terence M. Jones,

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CCC publication: Permanent Hair Loss Associated with Taxane Chemotherapy Use in Breast Cancer: a Retrospective Review at Two Tertiary UK Cancer Centres,

Citation: Clinical Oncology. 2020, 32(8), e167 (Conference Abstract) European Journal of Cancer Care. 2021, 30(3), 1-8

Author: H. Adderley, J. Chan, M. Alameddine, C. Kelly, Z. Salih, K.H.J. Lim, R. Fox, C. Tetlow, D. Arundell, H. Wong, M. Harries, A. Armstrong, N. Thorp,

Abstract: PURPOSE: Taxane chemotherapy is commonly used in the management of breast cancer. Hair loss (alopecia) is an expected side effect which may have a significant effect on quality of life. Alopecia is normally temporary but permanent chemotherapy-induced alopecia (pCIA) is increasingly recognised especially following docetaxel chemotherapy. However, the prevalence following docetaxel is not well understood and there is no published literature for paclitaxel chemotherapy. The aim of this study is to investigate the prevalence and patterns of pCIA resulting from both docetaxel and paclitaxel chemotherapy at two tertiary UK cancer centres. METHODS: In collaboration between Clatterbridge Cancer Centre and The Christie NHS Foundation Trusts, a retrospective survey was conducted for breast cancer patients who had received taxane chemotherapy in the neoadjuvant and adjuvant settings. Patients who had concluded chemotherapy at least a year previously were contacted by post and invited to participate by completing a questionnaire and returning it to their treatment centre. Data collected included the incidence and pattern of pCIA using the Savin pictorial hair loss scale, and the methods used by patients to manage it. Fisher's exact test was used to comparepCIA between the docetaxel and paclitaxel cohorts. RESULTS: 383 patients responded to the survey (a 63.3% overall response rate). These comprised 245 patients receiving docetaxel and 138 patients treated with paclitaxel. pCIA was reported by 23.3% of patients receiving docetaxel and 10.1% paclitaxel (p < 0.01). Overall 16.7% of patients in both groups reported the ongoing use of products or appliances such as wigs to camouflage their pCIA. In the docetaxel group, pCIA appeared to be more frequent in post-menopausal women than peri- or pre-menopausal women (37.8%, 12.3% and 19.6% respectively [Chi-square test p < 0.01]). Also in the docetaxel group, there appeared to be a trend for more severe scalp alopecia when the patient also received an aromatase inhibitor (AI) or tamoxifen and this difference was most marked in those who had received both an AI and tamoxifen as components of their treatment regime (p = 0.04). The use of scalp cooling was only recorded in the Christie paclitaxel group (n = 12). Of these 12 patients, 83.3% reported no hair loss. While overall rates of permanent eyebrow, eyelash and nostril hair loss were low, this pattern of hair loss appeared more frequent in the paclitaxel than the docetaxel group 4.3% vs. 1.8% (p = 0.29). CONCLUSIONS: Both docetaxel and paclitaxel may cause permanent scalp hair loss, but it is significantly more prevalent with docetaxel compared with paclitaxel. IMPLICATIONS FOR CANCER SURVIVORS: Clinicians should counsel patients regarding the risk of permanent alopecia prior to embarking upon taxane chemotherapy and routinely offer scalp cooling if available. More research is required to understand the pathobiology of this important and previously under recognised long-term side effect to enable more active preventive and management approaches.

WUTH publication: Human Papilloma Virus (HPV) status may impact treatment outcomes in patients with pre-cancerous penile lesions (an eUROGEN Study)

Citation: International Journal of Impotence Research. 2020 Jul 24. Online ahead of print
Author: Ashley S, Shanks JH, Oliveira P, Lucky M, Parnham A, Lau M, Sangar V
Abstract: Penile intra-epithelial neoplasia (PeIN) is a known precursor for penile cancer. It may be undifferentiated or differentiated. The former is related to high-risk Human Papilloma Virus (HPV) and associated with p16 over-expression. Patients may present with red patches or lesions on the penis which on occasion may affect sexual activity.This study will assess associations between p16 status, patient parameters, treatment choice and outcomes. Data were collected on patients diagnosed with PeIN, who were referred to a single European Network, between 2008 and 2018. The following parameters were collected utilising patient records: demographics, smoking status, performance status, comorbidities, HPV/p16 status, lichen sclerosus (LS) status, treatment and clinical response. Log rank, Kaplan-Meier, Pearson Chi-Squared and Fishers Exact test were utilised to determine significance. One hundred thirty-seven patients were identified with PeIN and no invasive cancer. Staining for p16 was available in 91 patients and 74 patients were p16+. There were no significant differences in disease-free survival (DFS) for smoking status, performance status, comorbidities and lichen sclerosus, although patients with lichen sclerosus tended to recur sooner. Overall, p16+ patients showed significantly better DFS over p16- patients (n = 67; 10.4 vs 7.4 months; p = 0.023). In p16+ patients receiving treatment with imiquimod alone or with surgery, response rates were 100% vs 54% without imiquimod (n = 56; p = 0.017). In p16- patients receiving treatment with imiquimod alone or with surgery, response rates were 100% vs 56% without imiquimod (n = 17; p = 0.99). Overall 13.6% of patients progressed to cancer. The results indicate treatment combinations with immunotherapy tend to provide better responses despite p16 status. Patients with p16+ disease have a longer disease-free survival. Approximately 14% of patients progress to invasive disease. However, given the limitations in this study, further research is required to confirm these findings.

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WUTH publication: The ACPGBI recommends pause for reflection on transanal total mesorectal excision

Citation: Colorectal Disease. 2020, 22(7), 745-48
Author: Fearnhead NS, Acheson AG, Brown SR, Hancock L, Harikrishnan A, Kelly SB, Maxwell-Armstrong CA, Sagar PM, Siddiqi S, Walsh CJ, Wheeler JMD, Abercrombie JF, Association of Coloproctology of Great Britain, Ireland (ACPGBI) Executive, Getting It Right First Time (GIRFT)

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WUTH publication: Beta-blockers for congestive heart failure in children

Citation: The Cochrane Databse of Systematic Reviews. 2020, 7, CD007037
Author: Alabed S, Sabouni A, Al Dakhoul S, Bdaiwi Y
Abstract: Background: Beta-blockers are an essential part of standard therapy in adult congestive heart failure and therefore, are expected to be beneficial in children. However, congestive heart failure in children differs from that in adults in terms of characteristics, aetiology, and drug clearance. Therefore, paediatric needs must be specifically investigated. This is an update of a Cochrane review previously published in 2009.
Objectives: To assess the effect of beta-adrenoceptor-blockers (beta-blockers) in children with congestive heart failure.
Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS up to November 2015. Bibliographies of identified studies were checked. No language restrictions were applied.
Selection criteria: Randomised, controlled, clinical trials investigating the effect of beta-blocker therapy on paediatric congestive heart failure.
Data collection and analysis: Two review authors independently extracted and assessed data from the included trials.
Main results: We identified four new studies for the review update; the review now includes seven studies with 420 participants. Four small studies with 20 to 30 children each, and two larger studies of 80 children each, showed an improvement of congestive heart failure with beta-blocker therapy. A larger study with 161 participants showed no evidence of benefit over placebo in a composite measure of heart failure outcomes. The included studies showed no significant difference in mortality or heart transplantation rates between the beta-blocker and control groups. No significant adverse events were reported with beta-blockers, apart from one episode of complete heart block. A meta-analysis of left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) data showed a very small improvement with beta-blockers. However, there were vast differences in the age, age range, and health of the participants (aetiology and severity of heart failure; heterogeneity of diagnoses and co-morbidities); there was a range of treatments across studies (choice of beta-blocker, dosing, duration of treatment); and a lack of standardised methods and outcome measures. Therefore, the primary outcomes could not be pooled in meta-analyses.
Authors' conclusions: There is not enough evidence to support or discourage the use of beta-blockers in children with congestive heart failure, or to propose a paediatric dosing scheme. However, the sparse data available suggested that children with congestive heart failure might benefit from beta-blocker treatment. Further investigations in clearly defined populations with standardised methodology are required to establish guidelines for therapy. Pharmacokinetic investigations of beta-blockers in children are also required to provide effective dosing in future trials.


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Health Education England North / NIHR BRIDGING SCHEME

After what has been a difficult time in the NHS over recent months we are happy announce that the HEE/NIHR Bridging Scheme is back!!! Applications for the next cohort will open on 1st August 2020.

 

This scheme is designed to help nurses, midwives, allied health professionals, pharmacists and healthcare scientists to build the strongest possible applications for a PhD or a post-doctoral level fellowship primarily, though not exclusively, within the NIHR Integrated Clinical Academic (ICA) programme.   It’s designed to help those want ‘to make a difference’ through high quality applied clinical research in pursuit of a research leadership role. If you are a clinician who wishes to develop a clinical academic career, then the scheme may offer the support you need. To be eligible for one of these personal awards you must be about to complete a masters degree or PhD, hold a professional registration and have begun to develop a research profile within an NHS organisation. We intend to commence the scheme in January 2021 (though this is yet to be confirmed by Health Education England) in order to align  the application and recruitment process with the NIHR fellowship application dates.   Enquiries and applications are invited from eligible professions working across the North West, North East and Yorkshire & Humber regions of England.   Further information and details on how to apply can be found on our website, please click here

WUTH publication: Long-term outcomes of real world 'watch and wait' data for rectal cancer after neoadjuvant chemoradiotherapy

Citation: Colorectal Disease. 2020 Jun 3. Online ahead of print.
Author: Simpson G, Hopley P, Wilson J, Day N, Haworth A, Montazeri A, Smith D, Titu L, Anderson J, Agbamu D, Walsh C
Abstract: Aim: A 'watch and wait' (W&W) strategy after neoadjuvant long-course chemoradiotherapy (NACRT) remains controversial. Whilst encouraging short-term data exist, the strategy will be judged on long-term data. We present long-term, real-world UK data from a single National Health Service trust.
Methods: An analysis was performed of a prospectively maintained W&W database over 9 years between 2010 and 2018. Outcome measures include incidence and time to regrowth and overall and disease-free survival.
Results: We diagnosed 563 rectal cancers in 9 years. In all, 283 patients underwent rectal resection (50.3%). NACRT was used in 155 patients for margin-threatened tumours on staging MRI. Forty-nine patients (31.6%) experienced either a 'near complete' or a complete clinical response (cCR) at their 10 weeks post-NACRT assessment (MRI and endoscopy). The median age was 69 years (range 44-83), and the male to female ratio was 32:17. The median follow-up was 38 months (range 12-96). The median tumour distance from the anal verge was 7 cm (1-15 cm). Twenty-two patients had a cCR on initial assessment and 27 patients had a 'near' cCR. Of those 27 who experienced a 'near' cCR, 17 (63%) progressed to cCR on repeat assessment and 10 (37%) did not. Of these 10 patients, seven underwent standard surgical resection and three were unfit for surgery. R0 for the seven with delayed resection was 100%. Of 39 patients (22 cCR and 17 'near' cCR who progressed to cCR) (25.2% of those receiving NACRT), six patients experienced local regrowth (15.4%). The median time to local regrowth was 29 months (15-60 months). One of these six patients underwent salvage abdominoperineal resection, one was advised to have contact radiotherapy and four opted against surgery and also had contact radiotherapy. The overall survival was 100% at 2 years and 90% at 5 years. Disease-free survival was 90.47% at 2 years and 74.8% at 5 years.
Conclusion: A W&W treatment strategy was employed safely in this patient cohort with acceptable rates of local regrowth and survival.
Keywords: complete response; neoadjuvant chemoradiotherapy; rectal cancer; watch and wait.


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WUTH publication: Radiomics: Quantitative Radiology transforming Oncology Care

Citation: The British Journal of Radiology. 2020, 93(1111), 20200333. Epub 2020 May 6
Author: Boon IS, Yap MH, Au Yong TPT, Boon CS


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WUTH publication: Randomized Trial of Ciprofloxacin Doxycycline and Hydroxychloroquine Versus Budesonide in Active Crohn's Disease

Citation: Digestive diseases and sciences. 2020 Jul 17. Online ahead of print. 
Author: Rhodes JM, Subramanian S, Flanagan PK, Horgan GW, Martin K, Mansfield J, Parkes M, Hart A, Dallal H, Iqbal T, Butterworth J, Culshaw K, Probert C
Abstract: Background: Increased mucosa-associated E. coli are present in Crohn's disease, but their role in pathogenesis is uncertain.
Aims: To assess efficacy and safety of an antibiotic/hydroxychloroquine combination effective against E. coli inside macrophages.
Methods: Adults with moderately active disease (CDAI > 220-450 plus C reactive protein ≥ 5 mg/l and/or fecal calprotectin > 250 μg/g) were randomized to receive (open-label) oral budesonide (Entocort CR 9 mg/day 8 weeks, 6 mg/day 2 weeks, 3 mg/day 2 weeks) or oral ciprofloxacin 500 mg bd, doxycycline 100 mg bd, hydroxychloroquine 200 mg tds for 4 weeks, followed by doxycycline 100 mg bd and hydroxychloroquine 200 mg tds for 20 weeks. Primary endpoints were remission (CDAI ≤ 150) at 10 weeks, remission maintained to 24 weeks, and remission maintained to 52 weeks. Patients not responding (CDAI fall by > 70) by 10 weeks were invited to crossover onto the alternative therapy.
Results: Fifty-nine patients were recruited across 8 sites. Including crossover, 39 patients received antibiotics/hydroxychloroquine and 39 received budesonide. At 10 weeks, 24 weeks, and 52 weeks on initial therapy, only 2/27, 2/27, and 1/27 were in remission on antibiotics/hydroxychloroquine compared with 8/32, 1/32, and 1/32 on budesonide (P = 0.092 at 10 weeks). Withdrawals by 10 weeks due to adverse events were seen in 15 receiving antibiotics/hydroxychloroquine and 6 budesonide. Results including crossover were more promising with 9/24 patients receiving antibiotics/hydroxychloroquine per protocol in remission by 24 weeks. No correlation was seen between response to antibiotics/hydroxychloroquine and ASCA/OmpC antibody status or disease location.
Conclusion: Overall results with this antibiotic/hydroxychloroquine combination were unimpressive, but long-term remission is seen in some patients and justifies further study.
Keywords: Antibiotics; Ciprofloxacin; Crohn’s disease; Doxycycline; E. coli; Hydroxychloroquine.


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WUTH publication: A Prospective Cohort Comparative Study of Rivaroxaban, Dabigatran, and Apixaban Oral Thromboprophylaxis in 2431 Hip and Knee Arthroplasty Patients: Primary Efficacy Outcomes and Safety Profile

Citation: The Journal of Arthroplasty. 2020, S0883-5403(20), 30676-8. Online ahead of print
Author: Highcock AJ, As-Sultany M, Finley R, Donnachie NJ
Abstract: Background: Direct oral anticoagulants (DOACs) have promised superior efficacy to low molecular weight heparins in the prevention of venous thromboembolism (VTE) in total hip and knee arthroplasty. However, there are concerns about raised associated bleeding and wound problems with these agents. This study aims to evaluate and compare the efficacy and safety of the 3 DOAC drugs: rivaroxaban, dabigatran and apixaban.
Methods: The primary outcome measures were rate of symptomatic VTE and major bleeding. Secondary outcome measures were wound healing problems and requirement for return to theater. A total of 2431 patients received one of the DOAC drugs as thromboprophylaxis following total hip arthroplasty (35 days) or total knee arthroplasty (14 days) between 2011 and 2015. Binary variables were compared between the 3 groups by using the chi-squared test or Fisher's exact test. Relative risks of selected primary and secondary end points were also calculated for the prespecified pairwise comparison.
Results: The overall symptomatic VTE rate was 2%. Rivaroxaban had a statistically significant superior efficacy for overall VTE prevention (0.8% vs 2.6%) compared with dabigatran (P < .01) and apixaban (P < .01), and deep vein thrombosis prevention (0.3% vs 2.2%) over dabigatran (P < .01). The overall rate of major bleeding was 1.2% with no significant difference observed between the 3 studied drugs.
Conclusion: All 3 drugs had symptomatic VTE rates comparable with low molecular weight heparin from the published literature. Rivaroxaban appears to have superior efficacy in VTE prevention over apixaban and dabigatran. No statistical difference was observed for major bleeding with any of the 3 agents.
Keywords: apixaban; dabigatran; rivaroxaban; total hip arthroplasty; total knee arthroplasty; venous thromboembolism.


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WUTH publication: An Evaluation of Continuous Subcutaneous Infusions Across Seven NHS Acute Hospitals: Is There Potential for 48-hour Infusions?

Citation: BMC palliative care. 2020, 19(1), 99
Author: Baker J, Dickman A, Mason S, Bickerstaff M, Jackson R, McArdle A, Lawrence I, Stephenson F, Paton N, Kirk J, Waters B, Ellershaw J
Abstract: Background: Continuous subcutaneous infusions (CSCIs) are commonly used in the United Kingdom as a way of administering medication to patients requiring symptom control when the oral route is compromised. These infusions are typically administered over 24 h due to currently available safety data. The ability to deliver prescribed medication by CSCI over 48 h may have numerous benefits in both patient care and health service resource utilisation. This service evaluation aims to identify the frequency at which CSCI prescriptions are altered at NHS Acute Hospitals.
Methods: Pharmacists or members of palliative care teams at seven acute NHS hospitals recorded anonymised prescription data relating to the drug combination(s), doses, diluent and compatibility of CSCIs containing two or more drugs on a daily basis for a minimum of 2 days, to a maximum of 7 days.
Results: A total of 1301 prescriptions from 288 patients were recorded across the seven sites, yielding 584 discrete drug combinations. Of the 584 combinations, 91% (n = 533) included an opioid. The 10 most-common CSCI drug combinations represented 37% of the combinations recorded. Median duration of an unchanged CSCI prescription across all sites was 2 days.
Conclusion: Data suggests medication delivered by CSCI over 48 h may be a viable option. Before a clinical feasibility study can be undertaken, a pharmacoeconomic assessment and robust chemical and microbiological stability data will be required, as will the assessment of the perceptions from clinical staff, patients and their families on the acceptability of such a change in practice.
Keywords: CSCI; Palliative therapy; Subcutaneous infusions.


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WUTH publication: Cancer Oligometastases Heterogeneity: Standardizing Nomenclature in Regard to Defining Oligometastatic Disease From a Radiation Oncology Perspective: An ESTRO-ASTRO Consensus Document

Citation: Radiotherapy and Oncology. 2020, 149, 247-48
Author: Boon IS, Yong TPTA, Boon CS


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WUTH publication: Sacrococcygeal Dimensions and Curvature Are Associated With Resection Quality in Rectal Cancer Excision

Citation: Techniques in Coloproctology. 2020 Jun 27. Online ahead of print
Author: Simpson G, Marks T, Blacker S, Smith D, Walsh C
Abstract: Background: Technical factors affect oncologic outcomes in rectal cancer surgery. The anatomy of the bony pelvis can affect technical aspects of surgery, but is seldom considered preoperatively. We performed a morphometric analysis of the bony pelvis in patients having rectal cancer resection to assess its effect on surgical specimen quality.
Methods: We performed a retrospective analysis of a prospectively maintained database of patients who had resection for rectal cancer from January 2014 to December 2017. Preoperative magnetic resonance imaging (MRI) and computed tomography (CT) images were accessed and measurements of sacrococcygeal distance, sacrococcygeal recess depth/area, sacrococcygeal angulation, anteroposterior pelvic inlet/outlet, pubic height and interspinous distance were made. Outcome measures included anatomical variation, operating time and mesorectal specimen grade. In patients having extra-levator abdominoperineal excision (eLAPE) with coccygectomy, the completeness of coccygeal resection was assessed by postoperative CT scan. Data were analysed using binomial and multinomial logistic regression and linear regression.
Results: One hundred and twenty-two consecutive rectal cancer resections were performed (39 open, 42 laparoscopic, 12 laparoscopic-converted and 29 robotic). The median age was 72 years (range: 29-88 years). The male:female ratio was 83:39. Eighty-one patients had anterior resection, 8 had low Hartmann's resection and 32 had APE. Of those who had APE, 21 had eLAPE (all with coccygectomy). Females had a larger pelvic inlet (female: 124.9 mm, male: 114.9 mm), interspinous diameter(female:112.8 mm, male:97.6 mm), sacrococcygeal depth (female:42.6 mm, 39.35 mm) and sacrococcygeal area recess than males (female: 3697 mm2, male: 3481.5 mm2). Males had a greater pubic height (female: 51.8 mm, male: 54.05 mm) and greater sacrococcygeal distance (female: 116.7 mm, male: 123.65 mm) than females. In patients having anterior resection, tumour distance from the anal verge (p = 0.004), sacrococcygeal distance (p = 0.006) and sacrococcygeal curvature (p = 0.002) were associated with specimen quality. In patients who had eLAPE, median preoperative coccygeal length was 41 mm (IQR: 35.1-45.5). The median length of coccygeal resection was 9 mm (IQR: 1-17.45 mm). The median length of coccyx remaining postoperatively was 33 mm (IQR: 21.35-39 mm).
Conclusions: Sacrococcygeal curvature and distance as well as tumour distance from the anal margin were associated with specimen quality in anterior resection. Coccygectomy was not performed as completely as surgeons thought. Surgeons should include sacrococcygeal bony anatomy in rectal cancer surgical planning to potentially improve outcomes in both anterior resection and eLAPE approaches.
Keywords: Bony pelvis; Pelvic volumetry; Rectal cancer.


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