Citation: Rheumatology Advances in Practice. 2019, 3(2)
Author: Cleary G, Pain C, McCann L, Mahmood K, Brookes-Fazakerley S, Robinson S, Walton R, Highcock A, Landes C, Barnes N, Roberts I, James L
Abstract: OBJECTIVES: Despite medical advances, life-changing articular damage may still occur in patients with JIA. We report a cohort with destructive arthropathy of the ankle treated by surgical arthrodiastasis.
METHODS: Eight patients (nine ankles) received arthrodiastasis by means of an Ilizarov frame between 2009 and 2013. Patient- and clinician-reported outcome measures were collated prospectively, with retrospective analysis of demographics, disease and pre-surgical treatment.
RESULTS: Pre-surgery, all patients received IA CS (mean 0.8 injections/year) and MTX (mean diagnosis to treatment 3.8 years; two of eight started within 3 months). Seven of eight patients received biologic drugs. Pain scores improved by 56 and 29% (P < 0.005) at 6 and 12 months post-frame removal. American Academy Orthopaedic Foot and Ankle Society ankle-hindfoot scale, Oxford Ankle Foot Questionnaire-Child and Oxford Ankle Foot Questionnaire-Parent scores improved by 171, 62 and 80%, respectively (P < 0.005) at 12 months post-frame removal. Patients remained satisfied with surgical treatment for a mean of 13.3 months. There was transient pin site infection in three patients, and all patients had radiological improvement in joint space.
CONCLUSION: Arthrodiastasis with an Ilizarov frame is a safe, well-tolerated technique that should be considered as a short-term joint-preserving procedure to improve pain and function when damage has occurred. Delays to systemic medical treatment in this cohort would be considered out-with standard modern practice but, although less prevalent, destructive ankle arthropathy continues to occur in JIA, and we believe this study to be relevant. The ankle is particularly susceptible to damage and, even if localized, should be treated early and aggressively with DMARDs and rapid progression to biologic therapies.
LEVELOF EVIDENCE: Level IV.
KEYWORDS: ankle; arthrodiastasis; functional outcome; juvenile idiopathic arthritis; pain
Link to PubMed record
Monday, 30 September 2019
Wednesday, 25 September 2019
CCC publication: Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
Citation: JAMA Surgery. 2019 Sep 4. [Epub ahead of print]
Author: Jones RP, Psarelli EE, Jackson R, Ghaneh P, Halloran CM, Palmer DH, Campbell F, Valle JW, Faluyi O, O'Reilly DA, Cunningham D6, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ting Y, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Lerch MM, Mayerle J, Tjaden C, Strobel O, Hackert T, Büchler MW, Neoptolemos JP; European Study Group for Pancreatic Cancer
Abstract: Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.
Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.
Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.
Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.
Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.
Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P = .03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P = .04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P = .27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P = .85 and P = .35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P = .03).
Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.
Trial Registration: Clinicaltrials.gov Identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434.
Link to PubMed record
Author: Jones RP, Psarelli EE, Jackson R, Ghaneh P, Halloran CM, Palmer DH, Campbell F, Valle JW, Faluyi O, O'Reilly DA, Cunningham D6, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ting Y, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Lerch MM, Mayerle J, Tjaden C, Strobel O, Hackert T, Büchler MW, Neoptolemos JP; European Study Group for Pancreatic Cancer
Abstract: Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.
Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.
Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.
Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.
Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.
Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P = .03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P = .04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P = .27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P = .85 and P = .35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P = .03).
Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.
Trial Registration: Clinicaltrials.gov Identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434.
Link to PubMed record
CCC publication: A phase II trial of cabazitaxel as second line chemotherapy in relapsed locally advanced and/or metastatic carcinoma of the penis
Citation: The Journal of International Medical Research. 2019, 47(10), 4664-72 Epub 2019 Sep 10
Author: Challapalli A, Pearson S, Mitra AV, Coe M, Thomson A, Elliott T, Kirkbride P, Pickering L, Kirk H, Foulstone E, Evans H, Bravo A, Bahl AK
Abstract: KEYWORDS: Advanced penile cancer; cabazitaxel; metastasis; objective response rate; overall survival; progression-free survival; second line chemotherapy
Link to PubMed record
Author: Challapalli A, Pearson S, Mitra AV, Coe M, Thomson A, Elliott T, Kirkbride P, Pickering L, Kirk H, Foulstone E, Evans H, Bravo A, Bahl AK
Abstract: KEYWORDS: Advanced penile cancer; cabazitaxel; metastasis; objective response rate; overall survival; progression-free survival; second line chemotherapy
Link to PubMed record
CCC publication: Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial
Citation: The Lancet. Oncology. 2019, 20(11), 1531-43
Author: Brand DH1, Tree AC2, Ostler P3, van der Voet H4, Loblaw A5, Chu W5, Ford D6, Tolan S7, Jain S8, Martin A9, Staffurth J10, Camilleri P11, Kancherla K12, Frew J13, Chan A14, Dayes IS15, Henderson D6, Brown S16, Cruickshank C16, Burnett S16, Duffton A17, Griffin C16, Hinder V16, Morrison K2, Naismith O18, Hall E16, van As N19; PACE Trial Investigators
Abstract: BACKGROUND: Localised prostate cancer is commonly treated with external-beam radiotherapy. Moderate hypofractionation has been shown to be non-inferior to conventional fractionation. Ultra-hypofractionated stereotactic body radiotherapy would allow shorter treatment courses but could increase acute toxicity compared with conventionally fractionated or moderately hypofractionated radiotherapy. We report the acute toxicity findings from a randomised trial of standard-of-care conventionally fractionated or moderately hypofractionated radiotherapy versus five-fraction stereotactic body radiotherapy for low-risk to intermediate-risk localised prostate cancer.
METHODS: PACE is an international, phase 3, open-label, randomised, non-inferiority trial. In PACE-B, eligible men aged 18 years and older, with WHO performance status 0-2, low-risk or intermediate-risk prostate adenocarcinoma (Gleason 4 + 3 excluded), and scheduled to receive radiotherapy were recruited from 37 centres in three countries (UK, Ireland, and Canada). Participants were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group, to conventionally fractionated or moderately hypofractionated radiotherapy (78 Gy in 39 fractions over 7·8 weeks or 62 Gy in 20 fractions over 4 weeks, respectively) or stereotactic body radiotherapy (36·25 Gy in five fractions over 1-2 weeks). Neither participants nor investigators were masked to allocation. Androgen deprivation was not permitted. The primary endpoint of PACE-B is freedom from biochemical or clinical failure. The coprimary outcomes for this acute toxicity substudy were worst grade 2 or more severe Radiation Therapy Oncology Group (RTOG) gastrointestinal or genitourinary toxic effects score up to 12 weeks after radiotherapy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, NCT01584258. PACE-B recruitment is complete and follow-up is ongoing.
FINDINGS: Between Aug 7, 2012, and Jan 4, 2018, we randomly assigned 874 men to conventionally fractionated or moderately hypofractionated radiotherapy (n=441) or stereotactic body radiotherapy (n=433). 432 (98%) of 441 patients allocated to conventionally fractionated or moderately hypofractionated radiotherapy and 415 (96%) of 433 patients allocated to stereotactic body radiotherapy received at least one fraction of allocated treatment. Worst acute RTOG gastrointestinal toxic effect proportions were as follows: grade 2 or more severe toxic events in 53 (12%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 43 (10%) of 415 patients in the stereotactic body radiotherapy group (difference -1·9 percentage points, 95% CI -6·2 to 2·4; p=0·38). Worst acute RTOG genitourinary toxicity proportions were as follows: grade 2 or worse toxicity in 118 (27%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 96 (23%) of 415 patients in the stereotactic body radiotherapy group (difference -4·2 percentage points, 95% CI -10·0 to 1·7; p=0·16). No treatment-related deaths occurred.
INTERPRETATION: Previous evidence (from the HYPO-RT-PC trial) suggested higher patient-reported toxicity with ultrahypofractionation. By contrast, our results suggest that substantially shortening treatment courses with stereotactic body radiotherapy does not increase either gastrointestinal or genitourinary acute toxicity.
FUNDING: Accuray and National Institute of Health Research.
Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
Link to PubMed record
Author: Brand DH1, Tree AC2, Ostler P3, van der Voet H4, Loblaw A5, Chu W5, Ford D6, Tolan S7, Jain S8, Martin A9, Staffurth J10, Camilleri P11, Kancherla K12, Frew J13, Chan A14, Dayes IS15, Henderson D6, Brown S16, Cruickshank C16, Burnett S16, Duffton A17, Griffin C16, Hinder V16, Morrison K2, Naismith O18, Hall E16, van As N19; PACE Trial Investigators
Abstract: BACKGROUND: Localised prostate cancer is commonly treated with external-beam radiotherapy. Moderate hypofractionation has been shown to be non-inferior to conventional fractionation. Ultra-hypofractionated stereotactic body radiotherapy would allow shorter treatment courses but could increase acute toxicity compared with conventionally fractionated or moderately hypofractionated radiotherapy. We report the acute toxicity findings from a randomised trial of standard-of-care conventionally fractionated or moderately hypofractionated radiotherapy versus five-fraction stereotactic body radiotherapy for low-risk to intermediate-risk localised prostate cancer.
METHODS: PACE is an international, phase 3, open-label, randomised, non-inferiority trial. In PACE-B, eligible men aged 18 years and older, with WHO performance status 0-2, low-risk or intermediate-risk prostate adenocarcinoma (Gleason 4 + 3 excluded), and scheduled to receive radiotherapy were recruited from 37 centres in three countries (UK, Ireland, and Canada). Participants were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group, to conventionally fractionated or moderately hypofractionated radiotherapy (78 Gy in 39 fractions over 7·8 weeks or 62 Gy in 20 fractions over 4 weeks, respectively) or stereotactic body radiotherapy (36·25 Gy in five fractions over 1-2 weeks). Neither participants nor investigators were masked to allocation. Androgen deprivation was not permitted. The primary endpoint of PACE-B is freedom from biochemical or clinical failure. The coprimary outcomes for this acute toxicity substudy were worst grade 2 or more severe Radiation Therapy Oncology Group (RTOG) gastrointestinal or genitourinary toxic effects score up to 12 weeks after radiotherapy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, NCT01584258. PACE-B recruitment is complete and follow-up is ongoing.
FINDINGS: Between Aug 7, 2012, and Jan 4, 2018, we randomly assigned 874 men to conventionally fractionated or moderately hypofractionated radiotherapy (n=441) or stereotactic body radiotherapy (n=433). 432 (98%) of 441 patients allocated to conventionally fractionated or moderately hypofractionated radiotherapy and 415 (96%) of 433 patients allocated to stereotactic body radiotherapy received at least one fraction of allocated treatment. Worst acute RTOG gastrointestinal toxic effect proportions were as follows: grade 2 or more severe toxic events in 53 (12%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 43 (10%) of 415 patients in the stereotactic body radiotherapy group (difference -1·9 percentage points, 95% CI -6·2 to 2·4; p=0·38). Worst acute RTOG genitourinary toxicity proportions were as follows: grade 2 or worse toxicity in 118 (27%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 96 (23%) of 415 patients in the stereotactic body radiotherapy group (difference -4·2 percentage points, 95% CI -10·0 to 1·7; p=0·16). No treatment-related deaths occurred.
INTERPRETATION: Previous evidence (from the HYPO-RT-PC trial) suggested higher patient-reported toxicity with ultrahypofractionation. By contrast, our results suggest that substantially shortening treatment courses with stereotactic body radiotherapy does not increase either gastrointestinal or genitourinary acute toxicity.
FUNDING: Accuray and National Institute of Health Research.
Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
Link to PubMed record
CCC publication: Putting patients first: an inventive service delivering cancer treatment at home
Citation: Journal of Comparative Effectiveness Research. 2019, 8(12), 951-60
Author: Yip, Frances; Zavery, Burhan; Poulter-Clark, Helen; Spencer, Joan
Abstract: Aim: This study evaluated the patient experience of receiving subcutaneous chemotherapy at home via a unique 'Cancer Treatment at Home' outreach service adapted by the UK Clatterbridge Cancer Centre NHS Foundation Trust. Patients & methods: The service involved using highly trained nurses to deliver cancer treatments to patients in their own homes. Patient outcomes were monitored over 12 months via the Systemic Anti-Cancer Therapy at Home (SACT) survey using handheld electronic devices. Results: Of the 56 participating cancer patients, 53 provided responses. Patients received subcutaneous trastuzumab, denosumab, pembrolizumab, fulvestrant and goserelin. Overall, 96% of respondents were 'very satisfied' and 4% 'satisfied' with the service. All respondents would recommend the service to others. Conclusion: The 'Cancer Treatment at Home' service has improved the patient experience for cancer care and has been recognized nationally for its achievements.
KEYWORDS: denosumab; home care service; oncology; questionnaire; survey; trastuzumab
Link to PubMed record
Author: Yip, Frances; Zavery, Burhan; Poulter-Clark, Helen; Spencer, Joan
Abstract: Aim: This study evaluated the patient experience of receiving subcutaneous chemotherapy at home via a unique 'Cancer Treatment at Home' outreach service adapted by the UK Clatterbridge Cancer Centre NHS Foundation Trust. Patients & methods: The service involved using highly trained nurses to deliver cancer treatments to patients in their own homes. Patient outcomes were monitored over 12 months via the Systemic Anti-Cancer Therapy at Home (SACT) survey using handheld electronic devices. Results: Of the 56 participating cancer patients, 53 provided responses. Patients received subcutaneous trastuzumab, denosumab, pembrolizumab, fulvestrant and goserelin. Overall, 96% of respondents were 'very satisfied' and 4% 'satisfied' with the service. All respondents would recommend the service to others. Conclusion: The 'Cancer Treatment at Home' service has improved the patient experience for cancer care and has been recognized nationally for its achievements.
KEYWORDS: denosumab; home care service; oncology; questionnaire; survey; trastuzumab
Link to PubMed record
WUTH publication: Application of artificial intelligence (AI) in Radiotherapy workflow: Paradigm shift in Precision Radiotherapy using Machine Learning
Citation: The British Journal of Radiology. 2019, 92 (1103), 20190716 Epub ahead of print]
Author: Boon IS, Au Yong TPT, Boon CS
Link to PubMed record
Author: Boon IS, Au Yong TPT, Boon CS
Link to PubMed record
WUTH publication: Insidious onset of headache, diplopia and Horner's syndrome: a rare case of petrous bone osteomyelitis
Citation: BMJ Case reports. 2019, 12(9), e231062
Author: Biart S, Panicker J
Abstract: We present an unusual case of skull base osteomyelitis in an 88-year-old woman. She presented with gradual onset unilateral headache and diplopia. On examination, there was evidence of a left-sided Horner's and ipsilateral sixth nerve palsy. In addition to persistent raised inflammatory markers, an MRI neck identified signal change in the petrous bone confirming a diagnosis of skull base osteomyelitis. Skull base osteomyelitis should be considered in presentations of subacute raised inflammatory markers in the context of ipsilateral cranial nerve signs.
© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.
KEYWORDS: cranial nerves; headache (including migraines); infection (neurology)
Link to PubMed record
Author: Biart S, Panicker J
Abstract: We present an unusual case of skull base osteomyelitis in an 88-year-old woman. She presented with gradual onset unilateral headache and diplopia. On examination, there was evidence of a left-sided Horner's and ipsilateral sixth nerve palsy. In addition to persistent raised inflammatory markers, an MRI neck identified signal change in the petrous bone confirming a diagnosis of skull base osteomyelitis. Skull base osteomyelitis should be considered in presentations of subacute raised inflammatory markers in the context of ipsilateral cranial nerve signs.
© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.
KEYWORDS: cranial nerves; headache (including migraines); infection (neurology)
Link to PubMed record
Tuesday, 17 September 2019
WUTH publication: Development and Maintenance of a Pleural Disease Service: Role of the "Pleurologist"
Citation: Seminars in respiratory and critical care medicine. 2019, 40(3), 297-304
Author: Cameron K, Teodoro D, Kasis A, Evison M
Abstract: Changes in the health care environment, increasing specialization, and the use of ultrasound have led to pleural diseases being managed by a select few. This article aims to look at the impact of current medical education paradigms, service structure, procedural education and role of the "pleurologist" in providing care to patients with pleural disease.
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Link to PubMed record
Author: Cameron K, Teodoro D, Kasis A, Evison M
Abstract: Changes in the health care environment, increasing specialization, and the use of ultrasound have led to pleural diseases being managed by a select few. This article aims to look at the impact of current medical education paradigms, service structure, procedural education and role of the "pleurologist" in providing care to patients with pleural disease.
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Link to PubMed record
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