Publications by authors named "Ann Henry"

90 Publications

IPEM Topical Report: An international IPEM survey of MRI use for external beam radiotherapy treatment planning.

Phys Med Biol 2021 Feb 25. Epub 2021 Feb 25.

Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND.

Introduction/background: Despite growing interest in Magnetic Resonance Imaging (MRI), integration in external beam radiotherapy (EBRT) treatment planning uptake varies globally. In order to understand the current international landscape of MRI in EBRT a survey has been performed in 11 countries. This work reports on differences and common themes identified.

Methods: A multi-disciplinary Institute of Physics and Engineering in Medicine (IPEM) working party modified a survey previously used in the UK to understand current practice using MRI for EBRT treatment planning, investigate how MRI is currently used and managed as well as identify knowledge gaps. It was distributed electronically within 11 countries: Australia, Belgium, Denmark, Finland, France, Italy, the Netherlands, New Zealand, Sweden, the UK and the USA.

Results: The survey response rate within the USA was <1% and hence these results omitted from the analysis. In the other 10 countries the survey had a median response rate of 77% per country. Direct MRI access, defined as either having a dedicated MRI scanner for radiotherapy (RT) or access to a radiology MRI scanner, varied between countries. France, Italy and the UK reported the lowest direct MRI access rates and all other countries reported direct access in ≥82% of centres. Whilst ≥83% of centres in Denmark and Sweden reported having dedicated MRI scanners for EBRT, all other countries reported ≤29%. Anatomical sites receiving MRI for EBRT varied between countries, with brain/prostate/head and neck being most common. Commissioning and QA of image registration and MRI scanners varied greatly, as did MRI sequences performed, staffing models and training given to different staff groups. The lack of financial reimbursement for MR was a consistent barrier for MRI implementation for RT for all countries and MR access was a reported important barrier for all countries except Sweden and Denmark.

Conclusion: No country has a comprehensive approach for MR in EBRT adoption and financial barriers are present worldwide. Variations between countries in practice/equipment/staffing models and training/QA/MRI sequences have been identified, and are likely to be due to differences in funding as well as a lack of consensus or guidelines in the literature. Access to dedicated MR for EBRT is limited in all but Sweden and Denmark, but in all countries there are financial challenges with ongoing per patient costs. Despite these challenges, significant interest exists in increasing MR guided EBRT planning over the next 5 years.
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http://dx.doi.org/10.1088/1361-6560/abe9f7DOI Listing
February 2021

IPEM topical report: guidance on the use of MRI for external beam radiotherapy treatment planning.

Phys Med Biol 2021 Jan 15. Epub 2021 Jan 15.

Cancer Research UK & EPSRC Cancer Imaging Centre, Royal Marsden Hospital and Institute of Cancer Research, MRI Unit, Downs Road, Sutton, SM2 5PT, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND.

This document gives guidance for multidisciplinary teams within institutions setting up and using an MRI-guided radiotherapy (RT) treatment planning service. It has been written by a multidisciplinary working group from the Institute of Physics and Engineering in Medicine (IPEM). Guidance has come from the experience of the institutions represented in the IPEM working group, in consultation with other institutions, as well as information taken from the literature. Guidance is only given for MRI acquired for external beam RT treatment planning in a CT-based workflow, i.e. when MRI is acquired and registered to CT with the purpose of aiding delineation of target or organ at risk volumes. MRI-only RT and other RT treatment types such as brachytherapy and gamma radiosurgery are not considered in scope here, although some of the major themes discussed are relevant. The aim was to produce guidance that will be useful for institutions who are setting up and using a dedicated MR scanner for RT (referred to as an MR-sim) and those who will have limited time on an MR scanner potentially managed outside of the RT department, often by radiology. Although not specifically covered in this document, there is an increase in the use of hybrid MRI-linac systems worldwide and brief comments are included to highlight any crossover with the early implementation of this technology. In this document, advice is given on introducing an RT workload onto a non-RT-dedicated MR scanner, as well as planning for installation of an MR scanner dedicated for RT. Next, practical guidance is given on the following, in the context of RT planning: training and education for all staff working in and around an MR scanner; RT patient set-up on an MR scanner; MRI sequence optimisation for RT purposes; commissioning and quality assurance (QA) to be performed on an MR scanner; and MRI to CT registration, including commissioning and QA.
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http://dx.doi.org/10.1088/1361-6560/abdc30DOI Listing
January 2021

Ten-year longitudinal health-related quality of life following iodine-125 brachytherapy monotherapy for localized prostate cancer.

J Contemp Brachytherapy 2020 Dec 16;12(6):540-546. Epub 2020 Dec 16.

Department of Clinical Oncology, Leeds Teaching Hospital NHS Trust, Leeds, UK.

Purpose: This prospective longitudinal study quantifies health-related quality of life (HRQoL) up to 10 years following permanent iodine-125 (I) prostate brachytherapy alone for localized prostate cancer.

Material And Methods: In total, 120 patients completed a validated expanded prostate cancer index composite (EPIC) questionnaire pre-treatment and at 8 time points after treatment (6 weeks, 6, 10, 18 months, and 2, 3, 5, 10 years). At each time point, clinically relevant small, moderate, and severe declines in HRQoL were defined as 0.2-0.5 SD, 0.5-0.8 SD, and > 0.8 SD of baseline function for each of urinary, bowel, and sexual domains, respectively.

Results: Response rates in the first two years were > 90%, but thereafter dropped to 75% and 48% at 5 and 10 years, respectively. 50 patients (41.6%) responded at all stages. Maximal deterioration in mean urinary and sexual summary scores was noted 6 weeks after implant, with severe urinary symptoms and moderate bowel/sexual symptoms. At 6 months, urinary and bowel quality of life (QoL) had improved to mild impairment, which then fully resolved at 10 months. Sexual QoL remained mildly impaired throughout the 10 years of follow-up. At 10 years, new mild impairment of urinary and bowel QoL was found.

Conclusions: Clinically mild changes in urinary, bowel, and sexual QoL are found 10 years after I monotherapy. The impairment in sexual function persists from treatment, but urinary and bowel symptoms are new at 10 years.
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http://dx.doi.org/10.5114/jcb.2020.101686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787209PMC
December 2020

A Systematic Review of Focal Ablative Therapy for Clinically Localised Prostate Cancer in Comparison with Standard Management Options: Limitations of the Available Evidence and Recommendations for Clinical Practice and Further Research.

Eur Urol Oncol 2021 Jan 8. Epub 2021 Jan 8.

Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK; University of Aberdeen, Aberdeen, UK. Electronic address:

Context: The clinical effectiveness of focal therapy (FT) for localised prostate cancer (PCa) remains controversial.

Objective: To analyse the evidence base for primary FT for localised PCa via a systematic review (SR) to formulate clinical practice recommendations.

Evidence Acquisition: A protocol-driven, PRISMA-adhering SR comparing primary FT (sub-total, focal, hemi-gland, or partial ablation) versus standard options (active surveillance [AS], radical prostatectomy [RP], or external beam radiotherapy [EBRT]) was undertaken. Only comparative studies with ≥50 patients per arm were included. Primary outcomes included oncological, functional, and quality-of-life outcomes. Risk of bias (RoB) and confounding assessments were undertaken. Eligible SRs were reviewed and appraised (AMSTAR) and ongoing prospective comparative studies were summarised.

Evidence Synthesis: Out of 1119 articles identified, four primary studies (1 randomised controlled trial [RCT] and 3 retrospective studies) recruiting 3961 patients and ten eligible SRs were identified. Only qualitative synthesis was possible owing to clinical heterogeneity. Overall, RoB and confounding were moderate to high. An RCT comparing vascular-targeted focal photodynamic therapy (PDT) with AS found a significantly lower rate of treatment failure at 2 yr with PDT. There were no differences in functional outcomes, although PDT was associated with worse transient adverse events. However, the external validity of the study was contentious. A retrospective study comparing focal HIFU with robotic RP found no significant differences in treatment failure at 3 yr, with focal HIFU having better continence and erectile function recovery. Two retrospective cohort studies using Surveillance, Epidemiology and End Results data compared focal laser ablation (FLA) against RP and EBRT, reporting significantly worse oncological outcomes for FLA. The overall data quality and applicability of the primary studies were limited because of clinical heterogeneity, RoB and confounding, lack of long-term data, inappropriate outcome measures, and poor external validity. Virtually all the SRs identified concluded that there was insufficient high-certainty evidence to make definitive conclusions regarding the clinical effectiveness of FT, with the majority of SRs judged to have a low or critically low confidence rating. Eight ongoing prospective comparative studies were identified. Ways of improving the evidence base are discussed.

Conclusions: The certainty of the evidence regarding the comparative effectiveness of FT as a primary treatment for localised PCa was low, with significant uncertainties. Until higher-certainty evidence emerges from robust prospective comparative studies measuring clinically meaningful outcomes at long-term time points, FT should ideally be performed within clinical trials or well-designed prospective cohort studies.

Patient Summary: We examined the literature to determine the effectiveness of prostate-targeted treatment compared with standard treatments for untreated localised prostate cancer. There was no strong evidence showing that focal treatment compares favourably with standard treatments; consequently, focal treatment is not recommended for routine standard practice.
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http://dx.doi.org/10.1016/j.euo.2020.12.008DOI Listing
January 2021

Stereotactic ablative body radiotherapy in patients with oligometastatic cancers: a prospective, registry-based, single-arm, observational, evaluation study.

Lancet Oncol 2021 01;22(1):98-106

The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London, UK.

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.

Funding: NHS England Commissioning through Evaluation scheme.
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http://dx.doi.org/10.1016/S1470-2045(20)30537-4DOI Listing
January 2021

Protocol for tumour-focused dose-escalated adaptive radiotherapy for the radical treatment of bladder cancer in a multicentre phase II randomised controlled trial (RAIDER): radiotherapy planning and delivery guidance.

BMJ Open 2020 12 31;10(12):e041005. Epub 2020 Dec 31.

Radiotherapy and Imaging, The Institute of Cancer Research, London, UK.

Introduction: Daily radiotherapy delivered with radiosensitisation offers patients with muscle invasive bladder cancer (MIBC) comparable outcomes to cystectomy with functional organ preservation. Most recurrences following radiotherapy occur within the bladder. Increasing the delivered radiotherapy dose to the tumour may further improve local control. Developments in image-guided radiotherapy have allowed bladder tumour-focused 'plan of the day' radiotherapy delivery. We aim to test within a randomised multicentre phase II trial whether this technique will enable dose escalation with acceptable rates of toxicity.

Methods And Analysis: Patients with T2-T4aN0M0 unifocal MIBC will be randomised (1:1:2) between standard/control whole bladder single plan radiotherapy, standard dose adaptive tumour-focused radiotherapy or dose-escalated adaptive tumour-focused radiotherapy (DART). Adaptive tumour-focused radiotherapy will use a library of three plans (small, medium and large) for treatment. A cone beam CT taken prior to each treatment will be used to visualise the anatomy and inform selection of the most appropriate plan for treatment.Two radiotherapy fractionation schedules (32f and 20f) are permitted. A minimum of 120 participants will be randomised in each fractionation cohort (to ensure 57 evaluable DART patients per cohort).A comprehensive radiotherapy quality assurance programme including pretrial and on-trial components is instituted to ensure standardisation of radiotherapy planning and delivery.The trial has a two-stage non-comparative design. The primary end point of stage I is the proportion of patients meeting predefined normal tissue constraints in the DART group. The primary end point of stage II is late Common Terminology Criteria for Adverse Events grade 3 or worse toxicity aiming to exclude a rate of >20% (80% power and 5% alpha, one sided) in each DART fractionation cohort. Secondary end points include locoregional MIBC control, progression-free survival overall survival and patient-reported outcomes.

Ethics And Dissemination: This clinical trial is approved by the London-Surrey Borders Research Ethics Committee (15/LO/0539). The results when available will be disseminated via peer-reviewed scientific journals, conference presentations and submission to regulatory authorities.

Trial Registration Number: NCT02447549; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-041005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780718PMC
December 2020

Clinical Outcomes of a Randomized Trial of Adaptive Plan-of-the-Day Treatment in Patients Receiving Ultra-hypofractionated Weekly Radiation Therapy for Bladder Cancer.

Int J Radiat Oncol Biol Phys 2020 Dec 11. Epub 2020 Dec 11.

The Institute of Cancer Research, London, United Kingdom.

Purpose: Hypofractionated radiation therapy can be used to treat patients with muscle-invasive bladder cancer unable to have radical therapy. Toxicity is a key concern, but adaptive plan-of the day (POD) image-guided radiation therapy delivery could improve outcomes by minimizing the volume of normal tissue irradiated. The HYBRID trial assessed the multicenter implementation, safety, and efficacy of this strategy.

Methods: HYBRID is a Phase II randomized trial that was conducted at 14 UK hospitals. Patients with T2-T4aN0M0 muscle-invasive bladder cancer unsuitable for radical therapy received 36 Gy in 6 weekly fractions, randomized (1:1) to standard planning (SP) or adaptive planning (AP) using a minimization algorithm. For AP, a pretreatment cone beam computed tomography (CT) was used to select the POD from 3 plans (small, medium, and large). Follow-up included standard cystoscopic, radiologic, and clinical assessments. The primary endpoint was nongenitourinary Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 (≥G3) toxicity within 3 months of radiation therapy. A noncomparative single stage design aimed to exclude ≥30% toxicity rate in each planning group in patients who received ≥1 fraction of radiation therapy. Local control at 3-months (both groups combined) was a key secondary endpoint.

Results: Between April 15, 2014, and August 10, 2016, 65 patients were enrolled (SP, n = 32; AP, n = 33). The median follow-up time was 38.8 months (interquartile range [IQR], 36.8-51.3). The median age was 85 years (IQR, 81-89); 68% of participants (44 of 65) were male; and 98% of participants had grade 3 urothelial cancer. In 63 evaluable participants, CTCAE ≥G3 nongenitourinary toxicity rates were 6% (2 of 33; 95% confidence interval [CI], 0.7%-20.2%) for the AP group and 13% (4 of 30; 95% CI, 3.8%-30.7%) for the SP group. Disease was present in 9/48 participants assessed at 3 months, giving a local control rate of 81.3% (95% CI, 67.4%-91.1%).

Conclusions: POD adaptive radiation therapy was successfully implemented across multiple centers. Weekly ultrahypofractionated 36 Gy/6 fraction radiation therapy is safe and provides good local control rates in this older patient population.
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http://dx.doi.org/10.1016/j.ijrobp.2020.11.068DOI Listing
December 2020

Patterns of Lymph Node Failure in Patients With Recurrent Prostate Cancer Postradical Prostatectomy and Implications for Salvage Therapies.

Adv Radiat Oncol 2020 Nov-Dec;5(6):1126-1140. Epub 2020 Aug 31.

Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.

Purpose: There is increasing use of radical prostatectomy to treat patients with high-risk prostate cancer. This has contributed toward a pathologic stage migration, and a greater number of patients are subsequently being diagnosed with biochemical failure. There is increasing use of advanced imaging techniques in the setting of biochemical failure, including positron emission tomography-computed tomography (PET-CT).

Methods And Materials: This critical literature review highlights the evidence for PET-CT in postprostatectomy biochemical failure and identifies sites of pelvic lymph node relapse in the setting of biochemical failure and the potential implications that the locations of these relapses may have for salvage therapies. Potential future directions are then considered.

Results: The optimal PET-CT tracer remains uncertain but there is increasing use of prostate-specific membrane antigen PET-CT for investigating sites of nodal metastasis at low prostate-specific antigen levels, and this is leading to a blurring of the biochemical and radiologic recurrence phases. The optimal therapeutic approach remains undefined, with current trials investigating postoperative radiation therapy to the whole pelvis in addition to the prostatic fossa, the use of PET-CT in the setting of biochemical recurrence to guide delivery of salvage radiation therapy, and, for patients with node-only relapsed prostate cancer, the addition of whole pelvis radiation therapy to metastasis-directed therapies such as stereotactic ablative radiotherapy.

Conclusions: The most appropriate target volume for salvage radiation therapy remains uncertain, and the findings of studies using PET-CT to map nodal recurrences suggest that there could be a role for extending whole pelvis radiation therapy volumes to increase coverage of superior nodal regions. The emerging fields of radiomics and radiogenomics could provide important prognostic information and aid decision making for patients with relapsed prostate cancer.
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http://dx.doi.org/10.1016/j.adro.2020.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718540PMC
August 2020

Multicentre, deep learning, synthetic-CT generation for ano-rectal MR-only radiotherapy treatment planning.

Radiother Oncol 2020 Nov 29;156:23-28. Epub 2020 Nov 29.

Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, United Kingdom; Radiotherapy Research Group, Leeds Institute of Medical Research, University of Leeds, United Kingdom.

Background And Purpose: Comprehensive dosimetric analysis is required prior to the clinical implementation of pelvic MR-only sites, other than prostate, due to the limited number of site specific synthetic-CT (sCT) dosimetric assessments in the literature. This study aims to provide a comprehensive assessment of a deep learning-based, conditional generative adversarial network (cGAN) model for a large ano-rectal cancer cohort. The following challenges were investigated; T2-SPACE MR sequences, patient data from multiple centres and the impact of sex and cancer site on sCT quality.

Method: RT treatment position CT and T2-SPACE MR scans, from two centres, were collected for 90 ano-rectal patients. A cGAN model trained using a focal loss function, was trained and tested on 46 and 44 CT-MR ano-rectal datasets, paired using deformable registration, respectively. VMAT plans were created on CT and recalculated on sCT. Dose differences and gamma indices assessed sCT dosimetric accuracy. A linear mixed effect (LME) model assessed the impact of centre, sex and cancer site.

Results: A mean PTV D95% dose difference of 0.1% (range: -0.5% to 0.7%) was found between CT and sCT. All gamma index (1%/1 mm threshold) measurements were >99.0%. The LME model found the impact of modality, cancer site, sex and centre was clinically insignificant (effect ranges: -0.4% and 0.3%). The mean dose difference for all OAR constraints was 0.1%.

Conclusion: Focal loss cGAN models using T2-SPACE MR sequences from multiple centres can produce generalisable, dosimetrically accurate sCTs for ano-rectal cancers.
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http://dx.doi.org/10.1016/j.radonc.2020.11.027DOI Listing
November 2020

Long-term multicentre experience of adjuvant radiotherapy for pN3 squamous cell carcinoma of the penis.

BJU Int 2020 Nov 29. Epub 2020 Nov 29.

Royal Marsden Hospital and the Institute of Cancer Research, London, UK.

Objective: To present the long-term adjuvant radiotherapy outcomes of patients with pN3 squamous cell carcinoma of the penis (SCCp) treated at two UK centres.

Patients And Methods: We conducted a retrospective audit of all pN3 SCCp patients, deemed suitable for adjuvant therapy by a specialist multidisciplinary team at St George's and Leeds Hospitals, who received adjuvant radiotherapy. Primary outcomes were recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). Secondary outcomes were time to adjuvant treatment, frequency of in-field recurrence, site and side of recurrence, and dose and schedule of radiotherapy.

Results: A total of 146 patients were included: 121 completed radiotherapy, 4 did not complete radiotherapy and 21 did not start it. The median (interquartile range [IQR]) age was 59 (54-70)years. The 5-year RFS was 51%, CSS was 51% and OS was 44%. Adjuvant radiotherapy was started at a median (IQR) of 75 (48-106) days. A dose of 45 Gy in 20 fractions was most commonly used. Of the 125 patients who started adjuvant treatment, 55 relapsed. Of these relapses, 30 occurred in an inguinal or pelvic nodal station and 26 of the 30 were in a radiation field. Relapses in 18 of the 55 cases were in visceral sites only and seven were in both nodal (non-irradiated sites) and visceral sites. Doses of <50 Gy were used more commonly before 2013 and higher doses (>50 Gy) were more commonly used after 2013.

Conclusions: Application of a standard radiotherapy protocol within a centralized supra-network setting has achieved survival outcomes that would appear better than those previously documented for either radiotherapy or chemotherapy in a cohort with solely pN3 disease. The addition of adjuvant chemotherapy may improve these outcomes further. These data suggest that adjuvant radiotherapy has a role to play in the management of men with pN3 SCCp.
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http://dx.doi.org/10.1111/bju.15309DOI Listing
November 2020

EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent.

Eur Urol 2021 Feb 7;79(2):243-262. Epub 2020 Nov 7.

Liverpool University Hospitals NHS Trust, Liverpool, UK.

Objective: To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on screening, diagnosis, and local treatment of clinically localised prostate cancer (PCa).

Evidence Acquisition: The panel performed a literature review of new data, covering the time frame between 2016 and 2020. The guidelines were updated and a strength rating for each recommendation was added based on a systematic review of the evidence.

Evidence Synthesis: A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. Risk-adapted screening should be offered to men at increased risk from the age of 45 yr and to breast cancer susceptibility gene (BRCA) mutation carriers, who have been confirmed to be at risk of early and aggressive disease (mainly BRAC2), from around 40 yr of age. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is performed, a combination of targeted and systematic biopsies must be offered. There is currently no place for the routine use of tissue-based biomarkers. Whilst prostate-specific membrane antigen positron emission tomography computed tomography is the most sensitive staging procedure, the lack of outcome benefit remains a major limitation. Active surveillance (AS) should always be discussed with low-risk patients, as well as with selected intermediate-risk patients with favourable International Society of Urological Pathology (ISUP) 2 lesions. Local therapies are addressed, as well as the AS journey and the management of persistent prostate-specific antigen after surgery. A strong recommendation to consider moderate hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term hormonal treatment.

Conclusions: The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for their use in clinical practice. These PCa guidelines reflect the multidisciplinary nature of PCa management.

Patient Summary: Updated prostate cancer guidelines are presented, addressing screening, diagnosis, and local treatment with curative intent. These guidelines rely on the available scientific evidence, and new insights will need to be considered and included on a regular basis. In some cases, the supporting evidence for new treatment options is not yet strong enough to provide a recommendation, which is why continuous updating is important. Patients must be fully informed of all relevant options and, together with their treating physicians, decide on the most optimal management for them.
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http://dx.doi.org/10.1016/j.eururo.2020.09.042DOI Listing
February 2021

Understanding and identifying ways to improve hospital-based cancer care and treatment for people with dementia: an ethnographic study.

Age Ageing 2021 01;50(1):233-241

Centre for Dementia Research, School of Health and Community Studies, Leeds Beckett University, Leeds, UK.

Background: Providing cancer care and treatment for ageing populations with complicating comorbidities like dementia is a growing global challenge. This study aimed to examine the hospital-based cancer care and treatment challenges and support needs of people with dementia, and identify potential ways to address these.

Methods: A two-site ethnographic study in England involving semi-structured interviews, observations and accompanying conversations, and medical record review. Participants (N = 58) were people with dementia and comorbid cancer (n = 17), informal caregivers (n = 22) and hospital staff (n = 19). Ethnographically informed thematic analysis was conducted.

Results: There was an accumulated complexity of living with both illnesses simultaneously. People with dementia and families could feel confused and uninformed due to difficulties understanding, retaining and using cancer information, which impacted their informed treatment decision-making. Dementia increased the complexity and burden of travelling to and navigating unfamiliar hospital environments, frequent lengthy periods of waiting in hospital, and self-managing symptoms and side-effects at home. Oncology staff were often working without the full picture, due to variable documenting of dementia in medical records, dementia training was limited, and time and resource pressures impeded the highly individualised, flexible cancer care required by people with dementia. Supportive family carers were crucial in enabling people with dementia to access, navigate and undergo cancer treatment and care.

Conclusions: Dementia complicates cancer care in a range of ways accumulating across the cancer pathway. Our findings suggest there are several strategies and interventions, which we list here, with potential to improve cancer care and treatment for people with dementia and their families.
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http://dx.doi.org/10.1093/ageing/afaa210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793597PMC
January 2021

Prostate Cancer Radiation Therapy Recommendations in Response to COVID-19.

Adv Radiat Oncol 2020 Nov 29;5(Suppl 1):26-32. Epub 2020 Oct 29.

Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.

Purpose: During a global pandemic, the benefit of routine visits and treatment of patients with cancer must be weighed against the risks to patients, staff, and society. Prostate cancer is one of the most common cancers radiation oncology departments treat, and efficient resource utilization is essential in the setting of a pandemic. Herein, we aim to establish recommendations and a framework by which to evaluate prostate radiation therapy management decisions.

Methods And Materials: Radiation oncologists from the United States and the United Kingdom rapidly conducted a systematic review and agreed upon recommendations to safely manage patients with prostate cancer during the COVID-19 pandemic. A RADS framework was created: remote visits, and avoidance, deferment, and shortening of radiation therapy was applied to determine appropriate approaches.

Results: Recommendations were provided by the National Comprehensive Cancer Network risk group regarding clinical node-positive, postprostatectomy, oligometastatic, and low-volume M1 disease. Across all prostate cancer stages, telemedicine consultations and return visits were recommended when resources/staff available. Delays in consultations and return visits of between 1 and 6 months were deemed safe based on stage of disease. Treatment can be avoided or delayed until safe for very low, low, and favorable intermediate-risk disease. Unfavorable intermediate-risk, high-risk, clinical node-positive, recurrence postsurgery, oligometastatic, and low-volume M1 disease can receive neoadjuvant hormone therapy for 4 to 6 months as necessary. Ultrahypofractionation is preferred for localized, oligometastatic, and low-volume M1, and moderate hypofractionation is preferred for postprostatectomy and clinical node positive disease. Salvage is preferred to adjuvant radiation.

Conclusions: Resources can be reduced for all identified stages of prostate cancer. The RADS (remote visits, and avoidance, deferment, and shortening of radiation therapy) framework can be applied to other disease sites to help with decision making in a global pandemic.
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http://dx.doi.org/10.1016/j.adro.2020.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598436PMC
November 2020

EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II-2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer.

Eur Urol 2021 Feb 7;79(2):263-282. Epub 2020 Oct 7.

Department of Urology, University Hospital, St. Etienne, France.

Objective: To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy & Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (CRPC).

Evidence Acquisition: The working panel performed a literature review of the new data (2016-2019). The guidelines were updated, and the levels of evidence and/or grades of recommendation were added based on a systematic review of the literature.

Evidence Synthesis: Prostate-specific membrane antigen positron emission tomography computed tomography scanning has developed an increasingly important role in men with biochemical recurrence after local therapy. Early salvage radiotherapy after radical prostatectomy appears as effective as adjuvant radiotherapy and, in a subset of patients, should be combined with androgen deprivation. New treatments have become available for men with metastatic hormone-sensitive prostate cancer (PCa), nonmetastatic CRPC, and metastatic CRPC, along with a role for local radiotherapy in men with low-volume metastatic hormone-sensitive PCa. Also included is information on quality of life outcomes in men with PCa.

Conclusions: The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are first endorsed by the EANM and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online (http://uroweb.org/guideline/prostate-cancer/).

Patient Summary: This article summarises the guidelines for the treatment of relapsing, metastatic, and castration-resistant prostate cancer. These guidelines are evidence based and guide the clinician in the discussion with the patient on the treatment decisions to be taken. These guidelines are updated every year; this summary spans the 2017-2020 period of new evidence.
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http://dx.doi.org/10.1016/j.eururo.2020.09.046DOI Listing
February 2021

A Single Centre Randomised Control Study to Assess the Impact of Pre-Operative Carbohydrate Loading on Women Undergoing Major Surgery for Epithelial Ovarian Cancer.

Cureus 2020 Aug 31;12(8):e10169. Epub 2020 Aug 31.

Gynaecology, Leeds Teaching Hospitals NHS Trust, Leeds, GBR.

Objective Historically, patients have fasted before elective surgery to ensure an empty stomach to avoid aspiration. A fasting-induced catabolic state however may adversely influence recovery after surgery. Our study was designed to test the effect of oral carbohydrate loading on clinical parameters in patients undergoing major surgery for advanced-stage ovarian cancer. Methods A double-blinded single-centre randomised trial was designed to recruit 110 patients with advanced-stage epithelial ovarian cancer undergoing either primary surgery, or neoadjuvant chemotherapy prior to debulking surgery. Following written informed consent, the patients were randomised into two groups. Group 1 received the carbohydrate drink (intervention) and group 2 received flavoured water (placebo). The quantity of fluid in both groups was 800ml the night before the surgery and 400ml two hours before the induction of anaesthesia. The primary endpoint of the study was the Length of Hospital Stay (LoHS); the secondary parameters assessed were pain scores, nausea and vomiting scores, bowel function, and postoperative complication rate. Results Between March 2009 and December 2011, 80 patients were randomised and 75 completed the study. A decision was made to close the trial early as a change in routine clinical practice meant that patients were admitted on the day of surgery rather than a day before. Analysis of the data revealed that there were no significant differences between the study groups in terms of LoHS and other clinical parameters. Conclusion In this single-center study, which failed to recruit the planned number of patients, we were unable to demonstrate that oral carbohydrate intake pre-operatively has significant impact on the recovery process or the length of hospitalisation postoperatively. Future studies should examine all aspects of an Enhanced Recovery Program after Surgery as a package as compared to a single element to enhance patient outcome.
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http://dx.doi.org/10.7759/cureus.10169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526975PMC
August 2020

PIVOTALboost: A phase III randomised controlled trial of prostate and pelvis versus prostate alone radiotherapy with or without prostate boost (CRUK/16/018).

Clin Transl Radiat Oncol 2020 Nov 1;25:22-28. Epub 2020 Sep 1.

Clinical Trials and Statistics Unit, The Institute of Cancer Research (ICR-CTSU), London, UK.

•PIVOTALboost evaluates benefits/toxicity of pelvic node RT and focal boost dose escalation.•Unfavourable intermediate/high risk and bulky local disease are most likely to benefit.•Functional MRI imaging is used to select patients for different types of dose escalation.•HDR brachytherapy or focal dose escalation with IMRT are used as options.•Training and support is provided to reduce variations of contouring and radiotherapy planning.•The trial is recruiting patients in 38 radiotherapy centres through the UK.
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http://dx.doi.org/10.1016/j.ctro.2020.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508714PMC
November 2020

Navigating cancer treatment and care when living with comorbid dementia: an ethnographic study.

Support Care Cancer 2020 Sep 21. Epub 2020 Sep 21.

Clinical Trials Research Unit, Institute of Clinical Trials Research, University of Leeds, Leeds, UK.

Objectives: The risks of developing cancer and dementia increase as we age; however, this comorbidity remains relatively under-researched. This study reports on the challenges that people affected by comorbid cancer and dementia face when navigating engagement with cancer treatment within secondary care.

Materials And Methods: An ethnographic study recruiting 17 people with cancer and dementia, 22 relatives and 19 oncology staff in two UK National Health Service Trusts. Observations (46 h) and informal conversations were conducted during oncology appointments involving people with dementia. Semi-structured interviews (n = 37) with people living with cancer and dementia, their relatives and staff working in various roles across oncology services were also carried out. Data were analysed using ethnographically informed thematic analysis.

Results: People with cancer and dementia experienced challenges across three areas of navigating cancer treatment and care: navigating through multiple services, appointments and layers of often complex information; repeatedly navigating transport to and from hospital; and navigating non-dementia-friendly hospital outpatient environments alongside the cognitive problems associated with dementia.

Conclusions: Dementia impacts patients' abilities to navigate the many practical aspects of attending hospital for cancer treatment and care. This study indicates the importance of addressing ways to improve the experience of travelling to and from the hospital, alongside extending the ongoing efforts to develop 'dementia-friendly' hospital in-patient areas and practices, to outpatient departments. Such steps will serve to improve hospital-based cancer treatment and care and more broadly outpatient appointment experiences for people with dementia and their families.
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http://dx.doi.org/10.1007/s00520-020-05735-zDOI Listing
September 2020

Decision-making in cancer care for people living with dementia.

Psychooncology 2020 08 7;29(8):1347-1354. Epub 2020 Jul 7.

Centre for Dementia Research, School of Health & Community Studies, Leeds Beckett University, Leeds, UK.

Objective: Increasing numbers of people are expected to live with comorbid cancer and dementia. Cancer treatment decision-making for these individuals is complex, particularly for those lacking capacity, requiring support across the cancer care pathway. There is little research to inform practice in this area. This ethnographic study reports on the cancer decision-making experiences of people with cancer and dementia, their families, and healthcare staff.

Methods: Participant observations, informal conversations, semi-structured interviews, and medical note review, in two NHS trusts. Seventeen people with dementia and cancer, 22 relatives and 19 staff members participated.

Results: Decision-making raised complex ethical dilemmas and challenges and raised concerns for families and staff around whether correct decisions had been made. Whose decision it was and to what extent a person with dementia and cancer was able to make decisions was complex, requiring careful and ongoing consultation and close involvement of relatives. The potential impact dementia might have on treatment understanding and toleration required additional consideration by clinicians when evaluating treatment options.

Conclusions: Cancer treatment decision-making for people with dementia is challenging, should be an ongoing process and has emotional impacts for the individual, relatives, and staff. Longer, flexible, and additional appointments may be required to support decision-making by people with cancer and dementia. Evidence-based decision-making guidance on how dementia impacts cancer prognosis, treatment adherence and efficacy is required.
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http://dx.doi.org/10.1002/pon.5448DOI Listing
August 2020

Corrigendum to 'EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort Under the Auspices of the EAU-ESMO Guidelines Committees' [European Urology 77 (2020) 223-250].

Authors:
J Alfred Witjes Marek Babjuk Joaquim Bellmunt H Maxim Bruins Theo M De Reijke Maria De Santis Silke Gillessen Nicholas James Steven Maclennan Juan Palou Tom Powles Maria J Ribal Shahrokh F Shariat Theo Van Der Kwast Evanguelos Xylinas Neeraj Agarwal Tom Arends Aristotle Bamias Alison Birtle Peter C Black Bernard H Bochner Michel Bolla Joost L Boormans Alberto Bossi Alberto Briganti Iris Brummelhuis Max Burger Daniel Castellano Richard Cathomas Arturo Chiti Ananya Choudhury Eva Compérat Simon Crabb Stephane Culine Berardino De Bari Willem De Blok Pieter J L De Visschere Karel Decaestecker Konstantinos Dimitropoulos Jose L Dominguez-Escrig Stefano Fanti Valerie Fonteyne Mark Frydenberg Jurgen J Futterer Georgios Gakis Bogdan Geavlete Paolo Gontero Bernhard Grubmüller Shaista Hafeez Donna E Hansel Arndt Hartmann Dickon Hayne Ann M Henry Virginia Hernandez Harry Herr Ken Herrmann Peter Hoskin Jorge Huguet Barbara A Jereczek-Fossa Rob Jones Ashish M Kamat Vincent Khoo Anne E Kiltie Susanne Krege Sylvain Ladoire Pedro C Lara Annemarie Leliveld Estefania Linares-Espinós Vibeke Løgager Anja Lorch Yohann Loriot Richard Meijer M Carmen Mir Marco Moschini Hugh Mostafid Arndt-Christian Müller Christoph R Müller James N'Dow Andrea Necchi Yann Neuzillet Jorg R Oddens Jan Oldenburg Susanne Osanto Wim J G Oyen Luís Pacheco-Figueiredo Helle Pappot Manish I Patel Bradley R Pieters Karin Plass Mesut Remzi Margitta Retz Jonathan Richenberg Michael Rink Florian Roghmann Jonathan E Rosenberg Morgan Rouprêt Olivier Rouvière Carl Salembier Antti Salminen Paul Sargos Shomik Sengupta Amir Sherif Robert J Smeenk Anita Smits Arnulf Stenzl George N Thalmann Bertrand Tombal Baris Turkbey Susanne Vahr Lauridsen Riccardo Valdagni Antoine G Van Der Heijden Hein Van Poppel Mihai D Vartolomei Erik Veskimäe Antoni Vilaseca Franklin A Vives Rivera Thomas Wiegel Peter Wiklund Peter-Paul M Willemse Andrew Williams Richard Zigeuner Alan Horwich

Eur Urol 2020 Jul 21;78(1):e48-e50. Epub 2020 May 21.

Emeritus Professor, The Institute of Cancer Research, London, UK.

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http://dx.doi.org/10.1016/j.eururo.2020.03.017DOI Listing
July 2020

Error detection thresholds for routine real time in vivo dosimetry in HDR prostate brachytherapy.

Radiother Oncol 2020 Aug 5;149:38-43. Epub 2020 May 5.

Leeds Cancer Centre, Leeds, UK.

Purpose: Routine real time in vivo dosimetry (IVD) is performed in HDR prostate brachytherapy to independently verify dose delivery. This study investigates impact of position uncertainty on error detection thresholds for IVD.

Methods: IVD is implemented using a microMOSFET placed centrally in the prostate using an additional needle. 144 IVD measurements were made for 15 Gy or 19 Gy single fraction treatments. Needle insertion and treatment planning used real-time trans-rectal ultrasound. Source-MOSFET position thresholds of ±1, ±2 and ±3 mm were used to calculate per-needle and total plan error detection thresholds for the measured dose using an uncertainty analysis based on the treatment plan data.

Results: The median dose difference from 144 total plan measurements was -5.2% (range +7.4% to -17.3%). 3 plans measured outside the total plan error detection threshold for position threshold ±1 mm, no plans measured outside the total plan error detection threshold for larger position thresholds. For 2233 individual needle measurements, for position thresholds of ±1 mm, ±2mm and ±3 mm the number of needles outside the per-needle error detection threshold was 103, 25 and 10 respectively and the number of treatments that would have required interruption based on these thresholds for real-time IVD was 66, 16 and 8 respectively.

Conclusion: IVD in HDR prostate brachytherapy using a microMOSFET provides a high level of confidence that we are correctly delivering the planned dose to our patients. A ±2-3 mm position threshold gives an appropriate balance between error detection and avoiding unnecessary treatment interruptions.
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http://dx.doi.org/10.1016/j.radonc.2020.04.058DOI Listing
August 2020

Efficacy and toxicity outcomes for patients treated with focal salvage high dose rate brachytherapy for locally recurrent prostate cancer.

Clin Transl Radiat Oncol 2020 Jul 27;23:20-26. Epub 2020 Mar 27.

Leeds Teaching Hospitals NHS Trust, Beckett Street, Leeds LS9 7TF, UK.

Introduction: Isolated local recurrence of prostate cancer following primary radiotherapy or brachytherapy may be treated with focal salvage high dose rate brachytherapy, although there remains an absence of high quality evidence to support this approach.

Methods: Men with prostate cancer treated consecutively between 2015 and 2018 using 19 Gy in a single fraction high dose rate brachytherapy (HDR) for locally recurrent prostate cancer were identified from an institutional database. Univariable analysis was performed to evaluate the relationship between patient, disease and treatment factors with biochemical progression free survival (bPFS).

Results: 43 patients were eligible for evaluation. Median follow up duration was 26 months (range 1-60). Median bPFS was 35 months (95% confidence interval 25.6-44.4). Kaplan-Meier estimates for bPFS at 1, 2 and 3 years post salvage were 95.2%, 70.6% and 41.8% respectively. On univariable Cox regression analysis, only nadir PSA was significantly associated with bPFS although the majority of patients were also treated with androgen deprivation therapy. Only one late grade 3 genitourinary toxicity was observed.

Conclusion: Focal salvage HDR brachytherapy may provide good biochemical control with a low risk of severe toxicity. Further evaluation within clinical trials are needed to establish its role in the management of locally recurrent prostate cancer.
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http://dx.doi.org/10.1016/j.ctro.2020.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186261PMC
July 2020

Prostate Cancer Radiation Therapy Recommendations in Response to COVID-19.

Adv Radiat Oncol 2020 Jul-Aug;5(4):659-665. Epub 2020 Apr 1.

Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.

Purpose: During a global pandemic, the benefit of routine visits and treatment of patients with cancer must be weighed against the risks to patients, staff, and society. Prostate cancer is one of the most common cancers radiation oncology departments treat, and efficient resource utilization is essential in the setting of a pandemic. Herein, we aim to establish recommendations and a framework by which to evaluate prostate radiation therapy management decisions.

Methods And Materials: Radiation oncologists from the United States and the United Kingdom rapidly conducted a systematic review and agreed upon recommendations to safely manage patients with prostate cancer during the COVID-19 pandemic. A RADS framework was created: remote visits, and avoidance, deferment, and shortening of radiation therapy was applied to determine appropriate approaches.

Results: Recommendations were provided by the National Comprehensive Cancer Network risk group regarding clinical node-positive, postprostatectomy, oligometastatic, and low-volume M1 disease. Across all prostate cancer stages, telemedicine consultations and return visits were recommended when resources/staff available. Delays in consultations and return visits of between 1 and 6 months were deemed safe based on stage of disease. Treatment can be avoided or delayed until safe for very low, low, and favorable intermediate-risk disease. Unfavorable intermediate-risk, high-risk, clinical node-positive, recurrence postsurgery, oligometastatic, and low-volume M1 disease can receive neoadjuvant hormone therapy for 4 to 6 months as necessary. Ultrahypofractionation is preferred for localized, oligometastatic, and low-volume M1, and moderate hypofractionation is preferred for postprostatectomy and clinical node positive disease. Salvage is preferred to adjuvant radiation.

Conclusions: Resources can be reduced for all identified stages of prostate cancer. The RADS (remote visits, and avoidance, deferment, and shortening of radiation therapy) framework can be applied to other disease sites to help with decision making in a global pandemic.
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http://dx.doi.org/10.1016/j.adro.2020.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118610PMC
April 2020

Enabling people with dementia to access and receive cancer treatment and care: The crucial role of supportive networks.

J Geriatr Oncol 2020 09 4;11(7):1125-1131. Epub 2020 Apr 4.

Clinical Trials Research Unit, Institute of Clinical Trials Research, University of Leeds, Leeds, UK. Electronic address:

Objectives: Despite cancer and dementia being conditions in which prevalence increases with age, there remains limited research on the cancer treatment and care needs of this population. Our study aimed to address this gap and this paper reports on the role of supportive networks in enabling people with dementia to access cancer treatment and care.

Materials And Methods: An ethnographic study involving seventeen people with cancer and dementia, 22 relatives and nineteen oncology staff. It comprised observations (46 h) of and informal conversations during oncology appointments attended by people with dementia and their relatives and semi-structured interviews (n = 37) with people living with cancer and dementia, their relatives and staff working in various roles across oncology services. Data were analysed using thematic analysis.

Results: Patients and oncology staff relied on and expected relatives to provide practical and emotional support around cancer treatment and care. Families varied in their ability to provide required support due to extent of the family network, practical issues, knowledge of the patient and their wishes, family conflict and the patient's willingness to accept help. Where no family network was available, support provision was complex and this could compromise access to cancer treatment.

Conclusions: People with comorbid cancer and dementia rely heavily on a supportive family network to access treatment and care. Oncology services need to assess the supportive networks available to individual patients in developing cancer treatment plans. Urgent consideration needs to be given to how those with no family networks can be appropriately supported.
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http://dx.doi.org/10.1016/j.jgo.2020.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544010PMC
September 2020

A history of transurethral resection of the prostate should not be a contra-indication for low-dose-rate I prostate brachytherapy: results of a prospective Uro-GEC phase-II trial.

J Contemp Brachytherapy 2020 Feb 28;12(1):1-5. Epub 2020 Feb 28.

Mount Vernon Cancer Centre, Northwood, United Kingdom.

Purpose: Early reports suggested that transurethral resection (TURP) prior to permanent seed brachytherapy (BT) results in high incontinence rates. Guidelines consider prior TURP as a contra-indication to treatment, but improvements in imaging and treatment planning may reduce this risk, and are investigated in this prospective study.

Material And Methods: 99 men with histologically proven low- to intermediate-risk, localized prostate cancer, with a history of TURP performed at least 3 months before BT procedure were enrolled. All patients received a permanent seed implant between March 2009 and June 2015. Intra-operative interactive planning was recommended to ensure optimal accuracy of seed placement during the procedure. No supplemental external beam was allowed. Target and organ at risk contouring, definition of clinical target volume (CTV), and dosimetric parameters followed the modified GEC-ESTRO guidelines for permanent seed implants, as described an earlier report of our group. Follow-up was scheduled every 3 months for the first year, and every 6 months afterwards, with minimum follow-up of 2 years.

Study Endpoints: The primary endpoint was the incidence of post-implant urinary incontinence. Secondary endpoints were the incidence of urinary and gastro-intestinal toxicity, the eventual impact on the sexual function, and the freedom from biochemical failure.

Results: The median follow-up time for these 99 patients was 49 months (min. 24, max. 96). In this series, the incontinence rate was 2% after TURP + BT and 2% in case of TURP + BT + re-TURP, ending up with a total urinary incontinence rate of 4%. Acute and late urinary toxicities were extremely low. No significant late gastro-intestinal toxicity was seen, and the 5-year biochemical non-evidence of disease (bNED) was 93%.

Conclusions: The excellent long-term results and low morbidity presented as well as many advantages of prostate brachytherapy over other treatments demonstrates that brachytherapy is an effective treatment for patients with transurethral resection and organ-confined prostate cancer.
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http://dx.doi.org/10.5114/jcb.2020.92913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073343PMC
February 2020

Current Treatment and Outcomes Benchmark for Locally Advanced or Metastatic Urothelial Cancer From a Large UK-Based Single Centre.

Front Oncol 2020 20;10:167. Epub 2020 Feb 20.

Leeds Cancer Centre, St James's University Hospital, Leeds, United Kingdom.

To characterize treatment patterns and survival outcomes for patients with locally advanced or metastatic malignancy of the urothelial tract during a period immediately preceding the widespread use of immune checkpoint inhibitors in the UK. We retrospectively examined the electronic case notes of patients attending the Leeds Cancer Center, UK with locally advanced or metastatic urothelial carcinoma, receiving chemotherapy between January 2003 and March 2017. Patient characteristics, treatment patterns, and outcomes were collected. Summary and descriptive statistics were calculated for categorical and continuous variables as appropriate. The Kaplan-Meier method was used to estimate median survival and Cox regression proportional hazards model was used to explore relationships between clinical variables and outcome. Two hundred and sixteen patients made up the study cohort, with a median age of 66 years (range: 35-83) and 72.7% being male. First-line treatment consisted of either a cisplatin- (44%) or carboplatin-based regimen (48%) in the majority of patients. Twenty seven percent of patients received a second-line of treatment (most commonly single-agent paclitaxel) following a first-line platinum containing regimen. Grade 4 neutropenia was observed in 19 and 27% of those treated with a first-line cisplatin- and carboplatin-based regimen, respectively. The median overall survival (mOS) of the study cohort was estimated to be 16.2 months (IQR: 10.6-28.3 months). Receipt by patients of cisplatin-based chemotherapy was associated with a longer mOS and this association persisted when survival analysis was adjusted for age, sex, performance status and presence of distant metastases. This study provides a useful benchmark for outcomes achieved in a real-world setting for patients with locally advanced or metastatic UC treated with chemotherapy in the immediate pre-immunotherapy era.
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http://dx.doi.org/10.3389/fonc.2020.00167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044411PMC
February 2020

Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer: An International Multidisciplinary Systematic Review.

Eur Urol 2020 05 4;77(5):614-627. Epub 2020 Mar 4.

Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany.

Context: The optimal treatment for men with high-risk localized or locally advanced prostate cancer (PCa) remains unknown.

Objective: To perform a systematic review of the existing literature on the effectiveness of the different primary treatment modalities for high-risk localized and locally advanced PCa. The primary oncological outcome is the development of distant metastases at ≥5 yr of follow-up. Secondary oncological outcomes are PCa-specific mortality, overall mortality, biochemical recurrence, and need for salvage treatment with ≥5 yr of follow-up. Nononcological outcomes are quality of life (QoL), functional outcomes, and treatment-related side effects reported.

Evidence Acquisition: Medline, Medline In-Process, Embase, and the Cochrane Central Register of Randomized Controlled Trials were searched. All comparative (randomized and nonrandomized) studies published between January 2000 and May 2019 with at least 50 participants in each arm were included. Studies reporting on high-risk localized PCa (International Society of Urologic Pathologists [ISUP] grade 4-5 [Gleason score {GS} 8-10] or prostate-specific antigen [PSA] >20 ng/ml or ≥ cT2c) and/or locally advanced PCa (any PSA, cT3-4 or cN+, any ISUP grade/GS) or where subanalyses were performed on either group were included. The following primary local treatments were mandated: radical prostatectomy (RP), external beam radiotherapy (EBRT) (≥64 Gy), brachytherapy (BT), or multimodality treatment combining any of the local treatments above (±any systemic treatment). Risk of bias (RoB) and confounding factors were assessed for each study. A narrative synthesis was performed.

Evidence Synthesis: Overall, 90 studies met the inclusion criteria. RoB and confounding factors revealed high RoB for selection, performance, and detection bias, and low RoB for correction of initial PSA and biopsy GS. When comparing RP with EBRT, retrospective series suggested an advantage for RP, although with a low level of evidence. Both RT and RP should be seen as part of a multimodal treatment plan with possible addition of (postoperative) RT and/or androgen deprivation therapy (ADT), respectively. High levels of evidence exist for EBRT treatment, with several randomized clinical trials showing superior outcome for adding long-term ADT or BT to EBRT. No clear cutoff can be proposed for RT dose, but higher RT doses by means of dose escalation schemes result in an improved biochemical control. Twenty studies reported data on QoL, with RP resulting mainly in genitourinary toxicity and sexual dysfunction, and EBRT in bowel problems.

Conclusions: Based on the results of this systematic review, both RP as part of multimodal treatment and EBRT + long-term ADT can be recommended as primary treatment in high-risk and locally advanced PCa. For high-risk PCa, EBRT + BT can also be offered despite more grade 3 toxicity. Interestingly, for selected patients, for example, those with higher comorbidity, a shorter duration of ADT might be an option. For locally advanced PCa, EBRT + BT shows promising result but still needs further validation. In this setting, it is important that patients are aware that the offered therapy will most likely be in the context a multimodality treatment plan. In particular, if radiation is used, the combination of local with systemic treatment provides the best outcome, provided the patient is fit enough to receive both. Until the results of the SPCG15 trial are known, the optimal local treatment remains a matter of debate. Patients should at all times be fully informed about all available options, and the likelihood of a multimodal approach including the potential side effects of both local and systemic treatment.

Patient Summary: We reviewed the literature to see whether the evidence from clinical studies would tell us the best way of curing men with aggressive prostate cancer that had not spread to other parts of the body such as lymph glands or bones. Based on the results of this systematic review, there is good evidence that both surgery and radiation therapy are good treatment options, in terms of prolonging life and preserving quality of life, provided they are combined with other treatments. In the case of surgery this means including radiotherapy (RT), and in the case of RT this means either hormonal therapy or combined RT and brachytherapy.
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http://dx.doi.org/10.1016/j.eururo.2020.01.033DOI Listing
May 2020

Lessons Learned From Introducing Staff to Quality Improvement Through Systematic Training at the Boston Public Health Commission.

J Public Health Manag Pract 2021 Mar-Apr 01;27(2):E100-E106

Office of Accreditation and Quality Improvement, Boston Public Health Commission, Boston, Massachusetts.

Context: The widespread adoption of quality improvement (QI) in public health departments holds the promise of transformational change for the American public health system; however, there is a lack of published literature pertaining to organization-level experiences with introductory QI training programs for health department staff. This practice report aims to share the innovative approach, experience, and results of introducing staff to QI principles at the Boston Public Health Commission (BPHC).

Program: The BPHC is an accredited health department that introduced more than 80% of its 1100 staff members to QI between January 2015 and December 2018. The commission's QI training program benefited from (1) visible support from senior leaders, (2) well-documented QI training plans, (3) innovative QI training curricula, (4) flexible delivery methods, and (5) a responsive monitoring and evaluation system.

Methods: To assess the effectiveness of QI training at the BPHC, participant questionnaires from QI training sessions (run between January 2015 and June 2018) and a separate questionnaire on organizational QI culture (administered to the supervisory staff in May 2018) were assessed using the Kirkpatrick model of training evaluation.

Evaluation: On the basis of Kirkpatrick's 4 levels of training effectiveness, 91% of participants were satisfied with training content (level 1), 94% of participants found the facilitators effective (level 2), 84% of participants indicated they would apply QI concepts in everyday work (level 3), and 75% of supervisors reported an organization-wide improvement in QI culture (level 4).

Discussion: These results show that the BPHC's QI training program has been resoundingly effective, with positive outcomes across all 4 levels of the Kirkpatrick model. These results reinforce the idea of the BPHC's experience as an exemplar for introductory QI training. Interested health departments should heed the lessons learned from this and other organizational experiences as they attempt to scale up QI competencies among staff members.
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http://dx.doi.org/10.1097/PHH.0000000000001102DOI Listing
February 2020

EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort: Under the Auspices of the EAU-ESMO Guidelines Committees.

Authors:
J Alfred Witjes Marek Babjuk Joaquim Bellmunt H Maxim Bruins Theo M De Reijke Maria De Santis Silke Gillessen Nicholas James Steven Maclennan Juan Palou Tom Powles Maria J Ribal Shahrokh F Shariat Theo Van Der Kwast Evanguelos Xylinas Neeraj Agarwal Tom Arends Aristotle Bamias Alison Birtle Peter C Black Bernard H Bochner Michel Bolla Joost L Boormans Alberto Bossi Alberto Briganti Iris Brummelhuis Max Burger Daniel Castellano Richard Cathomas Arturo Chiti Ananya Choudhury Eva Compérat Simon Crabb Stephane Culine Berardino De Bari Willem De Blok Pieter J L De Visschere Karel Decaestecker Konstantinos Dimitropoulos Jose L Dominguez-Escrig Stefano Fanti Valerie Fonteyne Mark Frydenberg Jurgen J Futterer Georgios Gakis Bogdan Geavlete Paolo Gontero Bernhard Grubmüller Shaista Hafeez Donna E Hansel Arndt Hartmann Dickon Hayne Ann M Henry Virginia Hernandez Harry Herr Ken Herrmann Peter Hoskin Jorge Huguet Barbara A Jereczek-Fossa Rob Jones Ashish M Kamat Vincent Khoo Anne E Kiltie Susanne Krege Sylvain Ladoire Pedro C Lara Annemarie Leliveld Estefania Linares-Espinós Vibeke Løgager Anja Lorch Yohann Loriot Richard Meijer M Carmen Mir Marco Moschini Hugh Mostafid Arndt-Christian Müller Christoph R Müller James N'Dow Andrea Necchi Yann Neuzillet Jorg R Oddens Jan Oldenburg Susanne Osanto Wim J G Oyen Luís Pacheco-Figueiredo Helle Pappot Manish I Patel Bradley R Pieters Karin Plass Mesut Remzi Margitta Retz Jonathan Richenberg Michael Rink Florian Roghmann Jonathan E Rosenberg Morgan Rouprêt Olivier Rouvière Carl Salembier Antti Salminen Paul Sargos Shomik Sengupta Amir Sherif Robert J Smeenk Anita Smits Arnulf Stenzl George N Thalmann Bertrand Tombal Baris Turkbey Susanne Vahr Lauridsen Riccardo Valdagni Antoine G Van Der Heijden Hein Van Poppel Mihai D Vartolomei Erik Veskimäe Antoni Vilaseca Franklin A Vives Rivera Thomas Wiegel Peter Wiklund Andrew Williams Richard Zigeuner Alan Horwich

Eur Urol 2020 02 19;77(2):223-250. Epub 2019 Nov 19.

Emeritus Professor, The Institute of Cancer Research, London, UK.

Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.

Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.

Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.

Setting: Online Delphi survey and consensus conference.

Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.

Outcome Measurements And Statistical Analysis: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).

Results And Limitations: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.

Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.

Patient Summary: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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http://dx.doi.org/10.1016/j.eururo.2019.09.035DOI Listing
February 2020

Using Multiparametric Magnetic Resonance Imaging to Shift Prostate Cancer Diagnosis Toward Clinically Significant Disease and Minimize Overdiagnosis (and Overtreatment).

Authors:
Ann Henry

Int J Radiat Oncol Biol Phys 2019 12;105(5):915-917

University of Leeds, St James University Hospital, Leeds, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.ijrobp.2019.09.040DOI Listing
December 2019