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Friday 29 November 2019

CCC publication: A randomised assessment of image guided radiotherapy within a phase 3 trial of conventional or hypofractionated high dose intensity modulated radiotherapy for prostate cancer

Citation: Radiotherapy and Oncology. 2020, 142, 62-71
Author: Murray, Julia; Griffin, Clare; Gulliford, Sarah; Syndikus, Isabel; Staffurth, John; Panades, Miguel; Scrase, Christopher; Parker, Chris; Khoo, Vincent; Dean, Jamie; Mayles, Helen; Mayles, Philip; Thomas, Simon; Naismith, Olivia; Baker, Angela; Mossop, Helen; Cruickshank, Clare; Hall, Emma; Dearnaley, David; CHHiP Investigators
Abstract: BACKGROUND AND PURPOSE: Image-guided radiotherapy (IGRT) improves treatment set-up accuracy and provides the opportunity to reduce target volume margins. We introduced IGRT methods using standard (IGRT-S) or reduced (IGRT-R) margins in a randomised phase 2 substudy within CHHiP trial. We present a pre-planned analysis of the impact of IGRT on dosimetry and acute/late pelvic side effects using gastrointestinal and genitourinary clinician and patient-reported outcomes (PRO) and evaluate efficacy.
MATERIALS AND METHODS: CHHiP is a randomised phase 3, non-inferiority trial for men with localised prostate cancer. 3216 patients were randomly assigned to conventional (74 Gy in 2 Gy/fraction (f) daily) or moderate hypofractionation (60 or 57 Gy in 3 Gy/f daily) between October 2002 and June 2011. The IGRT substudy included a second randomisation assigning to no-IGRT, IGRT-S (standard CTV-PTV margins), or IGRT-R (reduced CTV-PTV margins). Primary substudy endpoint was late RTOG bowel and urinary toxicity at 2 years post-radiotherapy.
RESULTS: Between June 2010 to July 2011, 293 men were recruited from 16 centres. Median follow-up is 56.9(IQR 54.3-60.9) months. Rectal and bladder dose-volume and surface percentages were significantly lower in IGRT-R compared to IGRT-S group; (p < 0.0001). Cumulative proportion with RTOG grade ≥ 2 toxicity reported to 2 years for bowel was 8.3(95% CI 3.2-20.7)%, 8.3(4.7-14.6)% and 5.8(2.6-12.4)% and for urinary 8.4(3.2-20.8)%, 4.6(2.1-9.9)% and 3.9(1.5-9.9)% in no IGRT, IGRT-S and IGRT-R groups respectively. In an exploratory analysis, treatment efficacy appeared similar in all three groups.
CONCLUSION: Introduction of IGRT was feasible in a national randomised trial and IGRT-R produced dosimetric benefits. Overall side effect profiles were acceptable in all groups but lowest with IGRT and reduced margins.
ISRCTN: 97182923.
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
KEYWORDS: Dosimetry; Image-guided radiotherapy; Prostate; Toxicity

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CCC publication: The efficacy and safety of venetoclax therapy in elderly patients with relapsed, refractory chronic lymphocytic leukaemia

Citation: British Journal of Haematology. 2019 Nov 4 [Epub ahead of print]
Author: Eyre, Toby A; Roeker, Lindsey E; Fox, Christopher P; Gohill, Satyen H; Walewska, Renata; Walter, Harriet S; Forconi, Francesco; Broom, Angus; Arumainathan, Arvind; Brander, Danielle M; Allan, John N; Schuster, Stephen J; Hill, Brian T; Lansigan, Frederick; Cheson, Bruce D; Lamanna, Nicole; Coombs, Catherine C; Barr, Paul M; Skarbnik, Alan P; Shadman, Mazyar; Ujjani, Chaitra S; Pearson, Laurie; Pagel, John M; Jacobs, Ryan; Mato, Anthony R
Abstract: Elderly chronic lymphocytic leukaemia (CLL) patients treated outside of trials have notably greater toxicity with the Bruton's tyrosine kinase inhibitor ibrutinib compared to younger patients. It is not known whether the same holds true for the B-cell lymphoma 2 inhibitor venetoclax. We provide a comprehensive analysis of key safety measures and efficacy in 342 patients comparing age categories ≥75 and <75 years treated in the relapsed, refractory non-trial setting. We demonstrate that venetoclax has equivalent efficacy and safety in relapsed/refractory CLL patients who are elderly, the majority of whom are previous ibrutinib-exposed and therefore may otherwise have few clear therapeutic options.
© 2019 British Society for Haematology and John Wiley & Sons Ltd.

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CCC publication: Reply to: Considerations on “impact of centralization of services on outcomes in a rare tumour: Retroperitoneal sarcomas”

Citation: European Journal of Surgical Oncology. 2020, 46(Part A), 708
Author: R. Kalaiselvan, A.K. Malik, R. Rao, K. Wong, N. Ali, M. Griffin, C.R. Chandrasekar, S.F. Fenwick, G.J. Poston, H. Malik,

CCC publication: CD8+ Tcell integrin alpha4beta7expression: A potential predictor of severity and steroid sensitivity in checkpoint inhibitor induced colitis

Citation: Journal for ImmunoTherapy of Cancer. 2019, 7
Author: Olsson-Brown A. (acob@liv.ac.uk); Sacco J.; Cachinho S.; Jolly C.; Fontana V.; Lord R.; Pirmohamed M.; Coles M.

CCC publication: Induction of serum CXCL10 by tebentafusp, a gp100-CD3 bispecific fusion protein, was associated with survival in uveal melanoma in a Phase I/II Study

Citation: Source Journal for ImmunoTherapy of Cancer. 2019, 7
Author: Butler M.; Higgs B. (brandon.higgs@immunocore.com); McAlpine C.; Sacco J.; Hassel J.; Abdullah S.; Ranade K.; Carvajal R.

CCC publication: Treatment beyond four cycles of first line Platinum and Etoposide chemotherapy in real-life patients with stage IV Small Cell Lung Cancer: a retrospective study of the Merseyside and Cheshire Cancer network

Citation: BMC pulmonary medicine. 2019, 19(1), 195
Author: Sallam, Mostafa; Wong, Helen; Escriu, Carles
Abstract: BACKGROUND: Dose intensity and dose density of first line Platinum and Etoposide (PE) do not influence Overall Survival (OS) of Small Cell Lung Cancer (SCLC) patients. The effect of treatment length, however, remains unclear. Current guidelines recommend treating beyond 4 cycles -up to 6-, in patients that respond to and tolerate systemic treatment. This has led to variable practice both in clinical practice and clinical research. Here we aimed at quantifying the possible clinical benefit of the extended regimen in our real-life patients treated with PE doublet.
METHODS: Of all patients with SCLC treated in our network with non-concurrent first line PE chemotherapy between 2008 and 2015, we identified and described patients that received 4 cycles (4c) or more (> 4c), and analysed patients with stage IV disease.
RESULTS: Two hundred forty-one patients with stage IV had 4c and 69 had > 4c. The latter were more likely to have sequential thoracic radiotherapy, which suggested a lower metastatic burden. Nevertheless, there were no statistically significant differences when comparing clinical outcomes. The median Duration of Response (DoR; time from last chemotherapy cycle to progression) was 5 months in both groups (HR 1.22; 95% CI 0.93-1.61). Median Progression Free Survival (PFS; time from diagnosis to radiological progression) was 8 months (4c) versus 9 months (> 4c) (HR 0.86; 95% CI 0.66-1.13) and median OS was 11 versus 12 months (HR 0.86, 95% CI 0.66-1.14).
CONCLUSION: Our results highlight a lack of clinical benefit by extending first line PE treatment in stage IV disease, and support limiting treatment to 4 cycles until superiority of a longer regimen is identified in a randomised study.
KEYWORDS: Antineoplastic combined chemotherapy protocols; Drug therapy; Lung neoplasm; Observational study; Small cell lung carcinoma

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CCC publication: Window of opportunity treatment in breast cancer

Citation: ANZ Journal of Surgery. 2019 Nov 26 [Epub ahead of print]
Author: Chen, Julia; Easwaralingam, Neshanth; Warrier, Sanjay; Ong, Andrew; Carson, Emma-Kate; Mak, Cindy; Snook, Kylie; Middleton, Kate; Parker, Andrew; Palmieri, Carlo; Spillane, Andrew; Mann, G Bruce; Lim, Elgene; Segara, Davendra
Abstract: Window of opportunity therapies, which involve short-term administration of systemic therapy between cancer diagnosis and surgery, have raised significant interest in recent years as a mean of assessing the sensitivity of a patient's cancer to therapy prior to surgery. There is now compelling evidence that in patients with early stage hormone-receptor positive breast cancer, a 2-week preoperative treatment with standard hormone therapies in a preoperative window period provides important prognostic information, which in turn helps to aid decision-making regarding treatment options. Changes in short-term biomarker endpoints such as cell proliferation measured by Ki-67 can act as surrogate markers of long-term outcomes. Paired tissues obtained pre- and post-investigational treatment, without having to subject the patient to additional biopsies, can then be used to conduct translational research to investigate predictive biomarkers and pharmacodynamics. In this review, we will examine the utility and challenges of window of opportunities therapies in breast cancer in the current literature, and the current Australian and international trial landscape in this clinical space.
© 2019 Royal Australasian College of Surgeons.

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CCC publication: Integrated treatment of brain metastases

Citation: Current Opinion in Oncology. 2019, 31(6), 501-7
Author: Rosenfelder N
Abstract: PURPOSE OF REVIEW: Optimal treatment of brain metastases has been limited to local treatment with few systemic options. Increasing use of systemic targeted therapies, chemotherapy and immunotherapy and combination of local and systemic treatments has resulted in plethora of publications. We review the existing evidence for individual treatments and new evidence for the integration of systemic and combination of local treatments.
RECENT FINDINGS: Encouraging efficacy of systemic therapies supports combination of systemic and local treatment albeit with little randomized trial data. Efficacy particularly of targeted agents provides an opportunity to delay local treatments including radiosurgery and whole brain radiotherapy. Randomized trials testing the integration of surgery, radiotherapy and radiosurgery are reviewed with emphasis on patient relevant endpoints to guide the clinician in the choice and sequence of treatments and integrating systemic and local therapies.
SUMMARY: There is increasing tendency to use focused radiation for single and oligometastases with or without surgery and decline in whole brain radiotherapy which is limited to multiple metastases in tumours without effective systemic options. Systemic therapies have promising intracranial efficacy and the sequence and combination with localized radiation is awaiting trials. Changes in practice with a move to primary systemic treatment for brain metastases without radiation, should be undertaken with caution and close monitoring.

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CCC publication: The First Supra-Regional Contact X-Ray Brachytherapy (Papillon) MDT: An Analysis of Treatment Decisions And Patient Choice

Citation: European Journal of Surgical Oncology. 2019, 45(11), 2222
Author: Fretwell V.; Wong H.; Myint A.S.

Monday 11 November 2019

WUTH publication: Breast conservation surgery by round block mammoplasty

Citation: European Journal of Surgical Oncology. 2020, 46(2) 240-44. Epub 2019 Oct 28
Author: Burrah R, James K, Lund J, Vinayagam R
Abstract: BACKGROUND: Round block mammoplasty (RBM) is a type of Oncoplastic procedure to facilitate breast conservation surgery for breast cancer.
METHODS: Retrospective study of 270 patients who underwent this surgery. The surgical and oncological outcomes of RBM were studied.
RESULTS: The median age was 61 years and median follow-up 39 months. Most cancers (59%) were screen-detected. The location of the cancer was commonly in the upper outer quadrant followed by upper inner quadrant (20%). The average tumor size was 18 mm and in 48% of patients the whole tumor size increased to 23.5 mm due to associated DCIS. The median specimen weight was 41 gm. Forty patients (14.8%) had positive margins. Postoperative complications were seen in 18 patients (6.6%). There were 4 local and 1 axillary recurrences, and 8 distant metastasis. Contralateral symmetrising surgery was required in 13 patients (4.8%).
CONCLUSION: RBM is a robust and easily adaptable technique which provides good exposure for a safe oncological excision. The surgical and oncological outcomes are good and contralateral symmetrising surgery is rarely required.
Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
KEYWORDS: Mammoplasty; Oncoplastic surgery; Round block

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Friday 8 November 2019

WUTH publication: A rare case of a diverticular perforation associated with colo-urachal fistula presenting as anaphylaxis

Citation: Annals of the Royal College of Surgeons of England. 2020, 102(3), e51-e53. Epub 2019 Nov 7.
Author: Yang D, Pearson D, Smith D
Abstract: Diverticular disease is a common clinical condition among Western populations, which increases with age. It can present in a variety of manners and has myriad of potential disease complications. We present a rare case of an adult patient with an extraperitoneal complications of a diverticular perforation presenting with facial swelling due to a colo-urachal fistula associated with a patent urachal remnant. Perforation should be considered in patients presenting with surgical emphysema with background of diverticular disease.
KEYWORDS: Colorectal surgery; Diverticular disease; Diverticular perforation; Surgical emphysema; Urachal remnant

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Tuesday 5 November 2019

WUTH publication: Medium-term outcome of posterior surgery in the treatment of non-tuberculous bacterial spinal infection

Citation: Journal of Orthopaedics. 2019, 16(6), 569-75
Author: Aljawadi A, Sethi G, Imo E, Arnall F, Choudhry MN, George KJ, Tambe A, Verma R, Yasin MN, Mohammed S, Siddique I
Abstract: OBJECTIVE: to evaluate the outcome of posterior spinal stabilization surgery for the management of bacterial spinal infection.
METHODS: 21 patients with bacterial infection were managed surgically with posterior stabilization. Outcome measures included neurological status. Follow-up data collected using Spine Tango COMI questionnaires and Euro Qol EQ-5D.
RESULTS: The mean improvement in neurological deficits was 0.91 Frankel grade. Residual symptoms of pain had no or minor effect on the work or usual activities in 52% of subjects, with 88% reported having either no or mid problems with mobility.
CONCLUSION: Posterior surgery can improve neurological outcome in approximately half of the patients.
© 2019 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.
KEYWORDS: Discitis; Infection; Spine; Spondylodiscitis; Surgery

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Monday 4 November 2019

WUTH publication: Training opportunities in thoracic ultrasound for respiratory trainees: are current guidelines practical?

Citation: BMJ open respiratory research. 2019, 6(1), e000390
Author: Stanton AE, Evison M, Roberts M, Latham J, Clive AO, Batalla-Duran E, Bhatnagar R, Asciak R, Diggins B, Bintcliffe OJ, Lees D, Parsonage M, Denny P, Gow K, Avram C, Gautam M, Rahman NM
Abstract: INTRODUCTION: Respiratory trainees in the UK face challenges in meeting current Royal College of Radiologists (RCR) Level 1 training requirements for thoracic ultrasound (TUS) competence, specified as attending 'at least one session per week over a period of no less than 3 months, with approximately five scans per session performed by the trainee (under supervision of an experienced practitioner)'. We aimed to clarify where TUS training opportunities currently exist for respiratory registrars.
METHODS: Data were collected (over a 4-week period) to clarify the number of scans (and therefore volume of training opportunities) within radiology departments and respiratory services in hospitals in the South West, North West deaneries and Oxford.
RESULTS: 14 hospitals (including three tertiary pleural centres) provided data. Of 964 scans, 793 (82.3%) were conducted by respiratory teams who performed a mean of 17.7 scans per week, versus 3.1 TUS/week in radiology departments. There was no radiology session in any hospital with ≥5 TUS performed, whereas 8/14 (86%) of respiratory departments conducted such sessions. Almost half (6/14) of radiology departments conducted no TUS scans in the period surveyed.
CONCLUSIONS: The currently recommended exposure of regularly attending a list or session to undertake five TUS is not achievable in radiology departments. The greatest volume of training opportunities exists within respiratory departments in a variety of scheduled and unscheduled settings. Revision of the competency framework in TUS, and where this is delivered, is required.
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
KEYWORDS: Imaging/CT MRI etc; pleural disease

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