Delphi consensus on stereotactic ablative radiotherapy for oligometastatic and oligoprogressive renal cell carcinoma-a European Society for Radiotherapy and Oncology study endorsed by the European Association of Urology.

The purpose of this European Society for Radiotherapy and Oncology (ESTRO) project, endorsed by the European Association of Urology, is to explore expert opinion on the management of patients with oligometastatic and oligoprogressive renal cell carcinoma by means of stereotactic ablative radiotherapy (SABR) on extracranial metastases, with the aim of developing consensus recommendations for patient selection, treatment doses, and concurrent systemic therapy. A questionnaire on SABR in oligometastatic renal cell carcinoma was prepared by a core group and reviewed by a panel of ten prominent experts in the field. The Delphi consensus methodology was applied, sending three rounds of questionnaires to clinicians identified as key opinion leaders in the field. At the end of the third round, participants were able to find consensus on eight of the 37 questions. Specifically, panellists agreed to apply no restrictions regarding age (25 [100%) of 25) and primary renal cell carcinoma histology (23 [92%] of 25) for SABR candidates, on the upper threshold of three lesions to offer ablative treatment in patients with oligoprogression, and on the concomitant administration of immune checkpoint inhibitor. SABR was indicated as the treatment modality of choice for renal cell carcinoma bone oligometatasis (20 [80%] of 25) and for adrenal oligometastases 22 (88%). No consensus or major agreement was reached regarding the appropriate schedule, but the majority of the poll (54%-58%) retained the every-other-day schedule as the optimal choice for all the investigated sites. The current ESTRO Delphi consensus might provide useful direction for the application of SABR in oligometastatic renal cell carcinoma and highlight the key areas of ongoing debate, perhaps directing future research efforts to close knowledge gaps.

Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer (IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised controlled trial.

BACKGROUND: A tumour-bed boost delivered after whole-breast radiotherapy increases local cancer-control rates but requires more patient visits and can increase breast hardness. IMPORT HIGH tested simultaneous integrated boost against sequential boost with the aim of reducing treatment duration while maintaining excellent local control and similar or reduced toxicity. METHODS: IMPORT HIGH is a phase 3, non-inferiority, open-label, randomised controlled trial that recruited women after breast-conserving surgery for pT1-3pN0-3aM0 invasive carcinoma from radiotherapy and referral centres in the UK. Patients were randomly allocated to receive one of three treatments in a 1:1:1 ratio, with computer-generated random permuted blocks used to stratify patients by centre. The control group received 40 Gy in 15 fractions to the whole breast and 16 Gy in 8 fractions sequential photon tumour-bed boost. Test group 1 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 48 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. Test group 2 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 53 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. The boost clinical target volume was the clip-defined tumour bed. Patients and clinicians were not masked to treatment allocation. The primary endpoint was ipsilateral breast tumour relapse (IBTR) analysed by intention to treat; assuming 5% 5-year incidence with the control group, non-inferiority was predefined as 3% or less absolute excess in the test groups (upper limit of two-sided 95% CI). Adverse events were assessed by clinicians, patients, and photographs. This trial is registered with the ISRCTN registry, ISRCTN47437448, and is closed to new participants. FINDINGS: Between March 4, 2009, and Sept 16, 2015, 2617 patients were recruited. 871 individuals were assigned to the control group, 874 to test group 1, and 872 to test group 2. Median boost clinical target volume was 13 cm3 (IQR 7 to 22). At a median follow-up of 74 months there were 76 IBTR events (20 for the control group, 21 for test group 1, and 35 for test group 2). 5-year IBTR incidence was 1·9% (95% CI 1·2 to 3·1) for the control group, 2·0% (1·2 to 3·2) for test group 1, and 3·2% (2·2 to 4·7) for test group 2. The estimated absolute differences versus the control group were 0·1% (-0·8 to 1·7) for test group 1 and 1·4% (0·03 to 3·8) for test group 2. The upper confidence limit for test group 1 versus the control group indicated non-inferiority for 48 Gy. Cumulative 5-year incidence of clinician-reported moderate or marked breast induration was 11·5% for the control group, 10·6% for test group 1 (p=0·40 vs control group), and 15·5% for test group 2 (p=0·015 vs control group). INTERPRETATION: In all groups 5-year IBTR incidence was lower than the 5% originally expected regardless of boost sequencing. Dose-escalation is not advantageous. 5-year moderate or marked adverse event rates were low using small boost volumes. Simultaneous integrated boost in IMPORT HIGH was safe and reduced patient visits. FUNDING: Cancer Research UK.

Invasive Burkholderia cepacia Complex Infections among Persons Who Inject Drugs, Hong Kong, China, 2016-2019.

During March 2016-January 2019, Burkholderia cepacia complex (BCC) infection developed in 13 persons who inject drugs (PWID) in Kowloon West Region, Hong Kong, China. Seven cases were infective spondylitis, 2 endocarditis, 2 septic arthritis, 1 intramuscular abscess and bacteremia, and 1 necrotizing fasciitis. Pulsed-field gel electrophoresis revealed that the isolates from 9 patients were clonally related. This clone caused major illness, and 11 of the 13 patients required surgical treatment. Clinicians should be aware of this pathogen and the appropriate broad-spectrum antimicrobial drugs to empirically prescribe for PWID with this life-threatening infection. Close collaboration among public health authorities, outreach social workers, and methadone clinics is essential for timely prevention and control of outbreaks in the PWID population.

Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial.

BACKGROUND: Local cancer relapse risk after breast conservation surgery followed by radiotherapy has fallen sharply in many countries, and is influenced by patient age and clinicopathological factors. We hypothesise that partial-breast radiotherapy restricted to the vicinity of the original tumour in women at lower than average risk of local relapse will improve the balance of beneficial versus adverse effects compared with whole-breast radiotherapy. METHODS: IMPORT LOW is a multicentre, randomised, controlled, phase 3, non-inferiority trial done in 30 radiotherapy centres in the UK. Women aged 50 years or older who had undergone breast-conserving surgery for unifocal invasive ductal adenocarcinoma of grade 1-3, with a tumour size of 3 cm or less (pT1-2), none to three positive axillary nodes (pN0-1), and minimum microscopic margins of non-cancerous tissue of 2 mm or more, were recruited. Patients were randomly assigned (1:1:1) to receive 40 Gy whole-breast radiotherapy (control), 36 Gy whole-breast radiotherapy and 40 Gy to the partial breast (reduced-dose group), or 40 Gy to the partial breast only (partial-breast group) in 15 daily treatment fractions. Computer-generated random permuted blocks (mixed sizes of six and nine) were used to assign patients to groups, stratifying patients by radiotherapy treatment centre. Patients and clinicians were not masked to treatment allocation. Field-in-field intensity-modulated radiotherapy was delivered using standard tangential beams that were simply reduced in length for the partial-breast group. The primary endpoint was ipsilateral local relapse (80% power to exclude a 2·5% increase [non-inferiority margin] at 5 years for each experimental group; non-inferiority was shown if the upper limit of the two-sided 95% CI for the local relapse hazard ratio [HR] was less than 2·03), analysed by intention to treat. Safety analyses were done in all patients for whom data was available (ie, a modified intention-to-treat population). This study is registered in the ISRCTN registry, number ISRCTN12852634. FINDINGS: Between May 3, 2007, and Oct 5, 2010, 2018 women were recruited. Two women withdrew consent for use of their data in the analysis. 674 patients were analysed in the whole-breast radiotherapy (control) group, 673 in the reduced-dose group, and 669 in the partial-breast group. Median follow-up was 72·2 months (IQR 61·7-83·2), and 5-year estimates of local relapse cumulative incidence were 1·1% (95% CI 0·5-2·3) of patients in the control group, 0·2% (0·02-1·2) in the reduced-dose group, and 0·5% (0·2-1·4) in the partial-breast group. Estimated 5-year absolute differences in local relapse compared with the control group were -0·73% (-0·99 to 0·22) for the reduced-dose and -0·38% (-0·84 to 0·90) for the partial-breast groups. Non-inferiority can be claimed for both reduced-dose and partial-breast radiotherapy, and was confirmed by the test against the critical HR being more than 2·03 (p=0·003 for the reduced-dose group and p=0·016 for the partial-breast group, compared with the whole-breast radiotherapy group). Photographic, patient, and clinical assessments recorded similar adverse effects after reduced-dose or partial-breast radiotherapy, including two patient domains achieving statistically significantly lower adverse effects (change in breast appearance [p=0·007 for partial-breast] and breast harder or firmer [p=0·002 for reduced-dose and p<0·0001 for partial-breast]) compared with whole-breast radiotherapy. INTERPRETATION: We showed non-inferiority of partial-breast and reduced-dose radiotherapy compared with the standard whole-breast radiotherapy in terms of local relapse in a cohort of patients with early breast cancer, and equivalent or fewer late normal-tissue adverse effects were seen. This simple radiotherapy technique is implementable in radiotherapy centres worldwide. FUNDING: Cancer Research UK.

Empowering radiation therapists: The role of an African Community of Practice in developing radiation Therapist education curriculum.

Objectives: Supported by the International Atomic Energy Agency (IAEA), the African Regional Cooperative Agreement for Research, Development and Training (AFRA) invited African Member States (MS) with a radiation therapy facility to engage in a 3-day workshop to develop a robust road map for educational standards in radiation therapist (RTT) training. The aim of the paper was to make recommendations of how the African MS could drive forward high educational standards in RTT training and education in Africa. Methods: A pre-workshop survey was developed and sent to the participants to gather background information on each MS's national RTT training standards. An online survey was sent to all African MS with a radiation therapy facility. Two international RTT education-training experts were tasked by the IAEA to support and facilitate the workshop, which consisted of presentations and discussions around the current RTT training schemes in African MS and aspects of modern training methodology. The agenda of the workshop was structured with the aim to simulate discussions on RTT education and training standards among participants from African MS. Results: Sixteen African MS completed the pre-workshop survey. The median number of radiotherapy centres within a MS was 3 (range 1--15). All MS provided two-dimensional radiation therapy services as a minimum while 75 % (12/16) MS could offer three-dimensional conformal radiation therapy service. Thirty-eight percent (6/16) reported that they had no radiation therapy machine service maintenance contracts with vendors and 56 % (9/16) MS had no biomedical engineers on site for unplanned and planned machine maintenance. The median number of RTTs at national level among MS was 23 (range 7-73). Fifty-six percent (9/16) MS had a RTT specific national training programme with 75 % (12/16) MS having clinical attachments for 6 months or more. Representatives from 12 African MS attended the AFRA workshop. An African Community of Practice (CoP) in developing Education Curriculum for RTT was established as an outcome of the workshop with the aim to facilitate knowledge exchange and drive quality initiatives among participating African MS. Four work streams were proposed to form the CoP: RTT academic qualifications, core competencies in RTT education and training, RTT education faculty composition and peer review process in RTT education curricula among African MS. Conclusion: By fostering collaboration, sharing knowledge, and advocating for improved policies, the African COP in developing Education Curriculum for RTT can make significant strides toward developing a RTT education curriculum that not only meets the unique challenges of the African continent but also aligns with global standards.

Treatment outcomes of stereotactic ablative body radiotherapy on oligometastases from colorectal cancer: early results of a single institution service evaluation.

Objective: Stereotactic ablative radiotherapy (SABR) has been suggested to be an effective non-invasive ablative therapy for oligometastases originated from colorectal cancer (CRC). This study aimed to report CRC oligometastases SABR treatment outcomes in terms of overall survival (OS), progression-free survival (PFS) and post-treatment toxicities. Methods: Treatment records of patients with CRC metachronous oligometastases who underwent SABR at a single institution between February 2015 and December 2018 were retrospectively reviewed. OS and PFS were calculated using Kaplan-Meier statistics and post-RT toxicity data was scored following CTCAE v. 4.0. Analysis of prognostic factors on OS and PFS was performed based on site of primary cancer, types of treatment to primary cancer, number of oligometastases, SABR treatment sites, intervals between treatment to primary cancer and SABR to oligometastases, biological equivalent dose, cumulative gross tumour volume and planning target volume. Results: 75 patients with 86 CRC metachronous oligometastases (including liver, lung, lymph nodes and bone) were included. The median age was 65.5 years (range 42.5-87.2) with a median follow-up of 23.8 months (range 3.1-46.5). The estimated median PFS was 14.6 months (95% CI 9.6-19.6). and estimated median OS was 33.3 months (95% CI 22.9-43.7). Majority of patients tolerated SABR well with the most common acute side-effects of Grade 1 fatigue. No Grade 3 or higher toxicities were reported at any time points.Only SABR treatment sites (p = 0.03) and cumulative volumes of planning target volume (p = 0.02) were found to be statistically significant independent predictors of PFS and OS respectively. Conclusion: This study showed modest PFS, OS, and post-treatment toxicity outcomes on SABR to metachronous oligometastases from CRC. It has highlighted that cumulative tumour volume may be a stronger prognostic factor of OS comparing to the number of metastases. Advances in knowledge: There are limited data published on the efficacy and post-treatment toxicity of CRC oligometastases SABR with adequate length of follow-up. Our retrospective study suggests that cumulative tumour volume may be a stronger prognostic factor of OS comparing to the number of oligometastases.

Reirradiation Options for Previously Irradiated Prostate cancer (RO-PIP): Feasibility study investigating toxicity outcomes following reirradiation with stereotactic body radiotherapy (SBRT) versus high-dose-rate brachytherapy (HDR-BT).

INTRODUCTION: Radiotherapy is the most common curative treatment for non-metastatic prostate cancer; however, up to 13% of patients will develop local recurrence within 10 years. Patients can undergo further and potentially curative treatment including salvage surgery, brachytherapy (BT), external beam radiotherapy, high-intensity focused ultrasound and cryotherapy. Systematic review shows that high-dose-rate (HDR) BT and stereotactic body radiotherapy (SBRT) have the best outcomes in terms of biochemical control and lowest side effects. The reirradiation options for previously irradiated prostate cancer (RO-PIP) trial aims to determine the feasibility of recruitment to a trial randomising patients to salvage HDR-BT or SBRT and provide prospective data on patient recorded toxicity outcomes that will inform a future phase III trial. METHODS AND ANALYSIS: The primary endpoint of the RO-PIP feasibility study is to evaluate the patient recruitment potential over 2 years to a trial randomising to either SBRT or HDR-BT for patients who develop local recurrence of prostate cancer following previous radiation therapy. The aim is to recruit 60 patients across 3 sites over 2 years and randomise 1:1 to SBRT or HDR-BT. Secondary objectives include recording clinician and patient-reported outcome measures to evaluate treatment-related toxicity. In addition, the study aims to identify potential imaging, genomic and proteomic biomarkers that are predictive of toxicity and outcome based on hypoxia status, a prognostic marker of prostate cancer. ETHICS AND DISSEMINATION: This study has been approved by the Yorkshire and The Humber-Bradford Leeds Research Ethics Committee (Reference: 21/YH/0305, IRAS: 297060, January 2022). The results will be presented in national and international conferences, published in peer-reviewed journals and will be communicated to relevant stakeholders. A plain English report will be shared with the study participants, patients' organisations and media. TRIAL REGISTRATION NUMBER: ISRCTN 12238218 (Amy Ackroyd NIHR CPMS Team).

High dose simultaneous integrated boost for node positive cervical cancer.

INTRODUCTION: Lymph node metastases presenting with locally advanced cervical cancer are poor prognostic features. Modern radiotherapy approaches enable dose escalation to radiologically abnormal nodes. This study reports the results of a policy of a simultaneous integrated boost (SIB) in terms of treatment outcomes. MATERIALS AND METHODS: Patients treated with radical chemoradiation with weekly cisplatin for locally advanced cervical cancer including an SIB to radiologically abnormal lymph nodes were analysed. All patients received a dose of 45 Gy in 25 fractions and a SIB dose of 60 Gy in 25 fractions using intensity modulated radiotherapy/volumetric modulated arc therapy, followed by high dose rate brachytherapy of 28 Gy in 4 fractions. A control cohort with radiologically negative lymph nodes was used to compare impact of the SIB in node positive patients. Treatment outcomes were measured by overall survival (OS), post treatment tumour response and toxicities. The tumour response was based on cross sectional imaging at 3 and 12 months and recorded as local recurrence free survival (LRFS), regional recurrence free survival (RRFS) and distant recurrence free survival (DRFS). RESULTS: In between January 2015 and June 2017, a total of 69 patients with a median follow up of 30.9 months (23 SIB patients and 46 control patients) were identified. The complete response rate at 3 months was 100% in the primary tumour and 83% in the nodal volume receiving SIB. The OS, LRFS, RRFS and DRFS at 3 years of the SIB cohort were 69%, 91%, 79% and 77% respectively. High doses can be delivered to regional pelvic lymph nodes using SIB without excessive toxicity. CONCLUSION: Using a SIB, a total dose of 60 Gy in 25 fractions chemoradiation can be delivered to radiologically abnormal pelvic nodes with no increase in toxicity compared to node negative patients. The adverse impact of positive nodal status may be negated by high dose deposition using SIB, but larger prospective studies are required to confirm this observation.

Future-proof Radiation therapist (RTT) practice in a pandemic - Lessons learnt from COVID-19.

BACKGROUND AND PURPOSE: The European SocieTy for Radiotherapy and Oncology Radiation Therapist Committee (ESTRO RTTC) published a guidance document and infographic providing recommendations to minimise risk of COVID-19 transmission in radiotherapy (RT) departments. The purpose of this study was to investigate the changes embedded in RT practice in the COVID-19 era and to recommend proactive measures to protect RT practice in future pandemics. MATERIALS AND METHODS: The study was initiated by the ESTRO Radiation Oncology Safety and Quality Committee (ROSQC). A survey consisting of multiple choice, open ended and Likert scale questions was created to analyse the extent of changes embedded in RT practice in response to the COVID-19 pandemic under the four domains: patient care, RTT workflow, remote working and RT practice. This online survey was distributed globally in May 2020. RESULTS: 229 respondents across 27 countries completed the survey. 60% of respondents reported continuing/commencing RT in COVID-19 patients. Routine testing of patients and RTTs was not common. Split teams' procedures, hot linacs and separate entrances were implemented by 50% of respondents. Remote working was implemented for RT team members where face to face patient contact was not essential. Lack of staff, connectivity issues and lack of confirmed positive cases in the department were the main reasons cited for not implementing recommended measures. CONCLUSION: It is suggested that RT departments have responded to the COVID-19 pandemic and implemented certain changes in RT practice. RT departments should act now to implement recommended proactive measures to protect patients and RTTs - frontline healthcare workers.

Ultra-hypofractionated radiotherapy for low- and intermediate risk prostate cancer: High-dose-rate brachytherapy vs stereotactic ablative radiotherapy.

PURPOSE: To compare the biochemical control rates (BCRs), late gastrointestinal (GI) and genitourinary (GU) toxicities in patients with low- and intermediate risk prostate cancer (PCa) treated with high-dose-rate brachytherapy (HDR BT) of 19 Gy/1 fraction, 26 Gy/2 fractions, or stereotactic ablative radiotherapy (SABR) of 36.25 Gy/5 fractions. METHODS AND MATERIALS: Between August 2008 and December 2017, patients with low- and intermediate risk PCa who received single dose or 2-fraction HDR BT, or 5-fraction SABR at a single institution were included. BCR for the whole population and the individual treatment groups were calculated using the Phoenix definition. Post treatment GI and GU toxicities were evaluated according to the CTCAE v4.0 guidelines. RESULTS: 185 patients with low- and intermediate risk PCa were included in this study with a median follow up of 60.5 months. BCRs at 3 and 5 years were 95% and 85% for all patients. The 5-year BCRs were 69%, 95% and 92% for the 19 Gy/1 fraction, 26 Gy/2 fractions and 36.25 Gy/5 fractions groups respectively. The cumulative 5-year incidence rates of ≥grade 2 GI events in the 19 Gy/1fr, 26 Gy/2fr and 36.25 Gy/5fr groups were 0%, 2% and 4%, respectively. Incidence rates in those treated in the 5-fraction SABR arm were significantly higher (p < 0.05) than those treated in both HDR BT arms where no statistically significant difference between the two HDR BT groups was seen (p = 0.15). The cumulative 5-year incidence rates of ≥grade 2 GU events in the 19 Gy/1fr, 26 Gy/2fr and 36.25 Gy/5fr groups were 30%, 5% and 6%, respectively. No statistically significant difference was found between the 26 Gy/2fr and 36.25 Gy/5fr (p = 0.37) treatment arms but the incidence rate in the 26 Gy/2fr were significantly lower than those seen after 19 Gy/1fr (p < 0.05). CONCLUSIONS: 26 Gy/2 fractions HDR BT provided equivalent BCR with lower toxicity compared to 36.25 Gy/5 fractions SABR. Both 2-fraction HBR BT and 5-fraction SABR achieved better BCRs than single dose 19 Gy HDR BT. The two-fraction HDR BT schedule should be considered as an important comparator in future clinical trials.

Thelaziasis as an uncommon cause of giant papillary conjunctivitis.

INTRODUCTION: We report a local human case of Thelazia callipaeda eye infection in a 49-year-old lady with history of fly contact in Hong Kong. CASE DESCRIPTION: A 49-year-old lady presented with right eye foreign body sensation for one month. She recalled a fly being stuck onto her right upper eyelashes with mascara when she went hiking in a forest trail in Hong Kong. On assessment there were a lot of giant papillae on palpebral conjunctiva. Three living worms crawling on conjunctiva were discovered and removed in total. The worms were identified as Thelazia callipaeda by morphology and molecular sequencing. After removal, her symptoms resolved completely. CONCLUSION: Human thelaziasis is probably under-reported in many countries. The presence of giant papillary conjunctivitis in non-contact lens wearers should alert clinicians to the possibility of thelaziasis in patients with compatible exposure history in endemic regions. Ophthalmologists should increase their awareness towards this uncommon disease and should not wrongly attributed the symptoms to allergic conjunctivitis.

A multicentre retrospective review of SABR reirradiation in rectal cancer recurrence.

BACKGROUND AND PURPOSE: Locally recurrent rectal cancer (LRRC) is associated with considerable morbidity, poor quality of life and an overall survival of 9 months. The non-operative treatment of LRRC is an understudied area, there is no consensus on management in this setting. We aim to perform a retrospective, multicentre analysis of patients treated with SABR reirradiation. MATERIALS AND METHODS: All patients were identified who received SABR re-irradiation for LRRC, at 3 UK centres, between August 2015 and September 2020. Eligible patients had pelvic recurrence and were either not suitable/opted not for surgery, or margin positive after exenturative surgery. Patients were treated with 30 Gy in 5 fractions and followed up with clinical review and CT scan at 3, 6, 12, 18 and 24 months. RESULTS: 69 patients with 81 lesions were identified and median follow up was 28 months. Median progression free survival (PFS) and overall survival (OS) were 12.1 months (10.4, 17.7) and 38.7 months (28.9,-) respectively. 2-year OS was 0.77 (0.66, 0.89). 58.3% of deaths were as a result of consequences of local relapse. 42.6% of patients had local relapse at death or last follow up. CONCLUSION: Our outcomes are encouraging for a population who had R1 resections, refused or were refused surgery; as they are similar to those in surgical series. Prospective data including details of survival, local relapse and QOL; with an optimised SABR technique, is required to establish SABR as an alternative to surgery.

An international Delphi consensus for pelvic stereotactic ablative radiotherapy re-irradiation.

INTRODUCTION: Stereotactic Ablative Radiotherapy (SABR) is increasingly used to treat metastatic oligorecurrence and locoregional recurrences but limited evidence/guidance exists in the setting of pelvic re-irradiation. An international Delphi study was performed to develop statements to guide practice regarding patient selection, pre-treatment investigations, treatment planning, delivery and cumulative organs at risk (OARs) constraints. MATERIALS AND METHODS: Forty-one radiation oncologists were invited to participate in three online surveys. In Round 1, information and opinion was sought regarding participants' practice. Guidance statements were developed using this information and in Round 2 participants were asked to indicate their level of agreement with each statement. Consensus was defined as ≥75% agreement. In Round 3, any statements without consensus were re-presented unmodified, alongside a summary of comments from Round 2. RESULTS: Twenty-three radiation oncologists participated in Round 1 and, of these, 21 (91%) and 22 (96%) completed Rounds 2 and 3 respectively. Twenty-nine of 44 statements (66%) achieved consensus in Round 2. The remaining 15 statements (34%) did not achieve further consensus in Round 3. Consensus was achieved for 10 of 17 statements (59%) regarding patient selection/pre-treatment investigations; 12 of 13 statements (92%) concerning treatment planning and delivery; and 7 of 14 statements (50%) relating to OARs. Lack of agreement remained regarding the minimum time interval between irradiation courses, the number/size of pelvic lesions that can be treated and the most appropriate cumulative OAR constraints. CONCLUSIONS: This study has established consensus, where possible, in areas of patient selection, pre-treatment investigations, treatment planning and delivery for pelvic SABR re-irradiation for metastatic oligorecurrence and locoregional recurrences. Further research into this technique is required, especially regarding aspects of practice where consensus was not achieved.

The implementation of an empty bladder filling protocol for localised prostate volumetric modulated arctherapy (VMAT): early results of a single institution service evaluation.

OBJECTIVE: To examine the impact of an empty bladder filling protocol on patients receiving radical RT for localised prostate cancer on post RT toxicity and biochemical progression free survival (bPFS). METHODS AND MATERIALS: Records of patients receiving radical external beam RT (EBRT) for localised prostate cancer with a full or empty bladder were reviewed. These included the bladder size on planning CT, daily online image guided RT (IGRT) setup data, treatment time and post treatment follow up data.These included bPFS, gastrointestinal(GI) and genitourinary(GU) toxicity scoring post RT using the CTCAE v4.0 scoring system. All patients included in the study were planned and treated under the same departmental clinical protocol with VMAT and daily online IGRT corrections. RESULTS: 90 patients were treated with 60 Gy in 20 fractions with a median follow up of 48 months. At 4 years bPFS in the empty bladder group was 100 and 98% in the full bladder group (p = 0.27). There were no statistically significant differences in cumulative ≥Grade 2GU (p = 0.10) and GI (p = 0.27) toxicity rates between the two bladder filling protocols. No statistically significant differences in the IGRT setup between the two groups of patients. Although the median treatment times per fraction were not statistically different between the two groups (p = 0.47), patients in the full bladder filling group were required to spend a longer time in the RT department per treatment session for bladder filling. CONCLUSION: An empty bladder filling protocol has non-inferior bPFS, GI and GU toxicities at 4 years in patients with localised prostate cancer using advanced RT techniques in comparison to a full bladder filling protocol. A longer follow up with a larger sample size is required to validate this approach. ADVANCES IN KNOWLEDGE: This study suggests that an empty bladder filling protocol can be used in external beam EBRT for localised prostate cancer with non-inferior treatment outcomes.

Meeting the challenges imposed by COVID-19: Guidance document by the ESTRO Radiation TherapisT Committee (RTTC).

COVID-19 - a novel coronavirus was firstly reported in December 2019. In response to threats imposed by COVID-19, the European society for radiotherapy and oncology Radiation TherapisT Committee (ESTRO RTTC) prepared this document in conjunction with an infographic with four main domains: patient care, RTT workflow, remote working and RT practice. In the context of the current COVID-19 pandemic, RTTs should be empowered with appropriate guidance and personal protection equipment in order to provide a safe radiotherapy service by limiting potential viral exposure to patients, healthcare workers and general public.

Automatic evaluation of contours in radiotherapy planning utilising conformity indices and machine learning.

BACKGROUND AND PURPOSE: Peer-review of Target Volume (TV) and Organ at Risk (OAR) contours in radiotherapy planning are typically conducted visually; this can be time consuming and subject to interobserver variation. This study investigated automatic evaluation of contouring using conformity indices and supervised machine learning. METHODS: A total of 393 contours from 253 Stereotactic Ablative Body Radiotherapy (SABR) benchmark cases (adrenal gland, liver, pelvic lymph node and spine), delineated by 132 clinicians from 25 centres, were visually evaluated for conformity against gold standard contours. Contours were scored as "pass" or "fail" on visual peer review and six Conformity Indices (CIs) were applied. CI values were mapped to pass/fail scores for each contour and used to train supervised machine learning models. A 5-fold cross validation method was employed to determine the predictive accuracies of each model. RESULTS: The stomach structure produced models with the highest predictive accuracy overall (96% using Support Vector Machine and Ensemble models), whilst the liver GTV produced models with the lowest predictive accuracy (76% using Logistic Regression). Predictive accuracies across all models ranged from 68-96% (68-87% for TV and 71-96% for OARs). CONCLUSIONS: Although a final visual review by an experienced clinician is still required, the automatic contour evaluation method could reduce the time for benchmark case reviews by identifying gross contouring errors. This method could be successfully implemented to support departmental training and the continuous assessment of outlining for clinical staff in the peer-review process, to reduce interobserver variability in contouring and improve interpretation of radiological anatomy.

A pilot study on dosimetric and radiomics analysis of urethral strictures following HDR brachytherapy as monotherapy for localized prostate cancer.

OBJECTIVE: A cohort of high dose-rate (HDR) monotherapy patients was analyzed to (i) establish the frequency of non-malignant urethral stricture; (ii) explore the relation between stricture formation with the dose distribution along the length of the urethra, and MRI radiomics features of the prostate gland. METHODS: A retrospective review of treatment records of patients who received 19 Gy single fraction of HDR brachytherapy (BT) was carried out. A matched pair analysis used one control for each stricture case matched with pre-treatment International Prostate Symptom Score (IPSS) score, number of needles used and clinical target volume volume for each stricture case identified.For all data sets, pre-treatment T2 weighted MRI images were used to define regions of interests along the urethra and within the whole prostate gland. MRI textural radiomics features-energy, contrast and homogeneity were selected. Wilcoxon signed-rank test was performed to investigate significant differences in dosimetric parameters and MRI radiomics feature values between cases and controls. RESULTS: From Nov 2010 to July 2017, there were 178 patients treated with HDR BT delivering 19 Gy in a single dose. With a median follow-up of 28.2 months, a total of 5/178 (3%) strictures were identified.10 patients were included in the matched pair analysis. The urethral dosimetric parameters investigated were not statistically different between cases and controls (p > 0.05). With regards to MRI radiomics feature analysis, significant differences were found in contrast and homogeneity between cases and controls (p < 0.05). However, this did not apply to the energy feature (p = 0.28). CONCLUSION: In this matched pair analysis, no association between post-treatment stricture and urethral dosimetry was identified. Our study generated a preliminary clinical hypothesis suggesting that the MRI radiomics features of homogeneity and contrast of the prostate gland can potentially identify patients who develop strictures after HDR BT. Although the sample size is small, this warrants further validation in a larger patient cohort. ADVANCES IN KNOWLEDGE: Urethral stricture has been reported as a specific late effect with prostate HDR brachytherapy. Our study reported a relatively low stricture rate of 3% and no association between post-treatment stricture and urethral dosimetry was identified. MRI radiomics features can potentially identify patients who are more prone to develop strictures.

Determination of cerebrospinal fluid adenosine deaminase activity cut-off for the diagnosis of tuberculous meningitis in Hong Kong.

AIMS: Tuberculous meningitis (TBM) is a severe infection which may lead to serious complication and mortality. Prompt diagnosis and treatment are essential. There is a need for a simple and fast laboratory test to differentiate TBM from other causes. METHODS: Retrospective review was conducted for cerebrospinal fluid adenosine deaminase (CSF-ADA) activity which was measured at the Chemical Pathology Laboratory of Princess Margaret Hospital, the sole centre providing such service in Hong Kong, for 51 patients with suspected meningitis from nine local hospitals between June 2014 and July 2017. TBM diagnosis was defined by positive culture and/or nucleic acid amplification test result of Mycobacterium tuberculosis complex in CSF. RESULTS: CSF-ADA activity was significantly higher in the TBM group (8.6±2.1 IU/L, n=8) than that of the non-TBM group (2.8±5.9 IU/L, n=43). The optimal clinical cut-off of 5.1 U/L for TBM diagnosis in our laboratory yielded 100% sensitivity, 91% specificity, positive likelihood ratio of 10.8 and negative likelihood ratio of 0. In rare circumstance, false elevation may be seen in non-tuberculous cause, such as central nervous system lymphoma and fungal infection. CONCLUSIONS: We recommend the use of CSF-ADA activity, which is a simple, fast and robust test for early differentiation of TBM from other causes, to facilitate timely initiation of antituberculous treatment and potentially improve patients' outcome.

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

PURPOSE: Previous studies of hypofractionated adjuvant whole-breast radiotherapy for early breast cancer established a 15- or 16-fraction (fr) regimen as standard. The FAST Trial (CRUKE/04/015) evaluated normal tissue effects (NTE) and disease outcomes after 5-fr regimens. Ten-year results are presented. METHODS: Women ≥ 50 years of age with low-risk invasive breast carcinoma (pT1-2 pN0) were randomly assigned to 50 Gy/25 fr (5 weeks) or 30 or 28.5 Gy in 5 once-weekly fr of 6.0 or 5.7 Gy. The primary end point was change in photographic breast appearance at 2 and 5 years; secondary end points were physician assessments of NTE and local tumor control. Odds ratios (ORs) from longitudinal analyses compared regimens. RESULTS: A total of 915 women were recruited from 18 UK centers (2004-2007). Five-year photographs were available for 615/862 (71%) eligible patients. ORs for change in photographic breast appearance were 1.64 (95% CI, 1.08 to 2.49; P = .019) for 30 Gy and 1.10 (95% CI, 0.70 to 1.71; P = .686) for 28.5 Gy versus 50 Gy. α/ß estimate for photographic end point was 2.7 Gy (95% CI, 1.5 to 3.9 Gy), giving a 5-fr schedule of 28 Gy (95% CI, 26 to 30 Gy) estimated to be isoeffective with 50 Gy/25 fr. ORs for any moderate/marked physician-assessed breast NTE (shrinkage, induration, telangiectasia, edema) were 2.12 (95% CI, 1.55 to 2.89; P < .001) for 30 Gy and 1.22 (95% CI, 0.87 to 1.72; P = .248) for 28.5 Gy versus 50 Gy. With 9.9 years median follow-up, 11 ipsilateral breast cancer events (50 Gy: 3; 30 Gy: 4; 28.5 Gy: 4) and 96 deaths (50 Gy: 30; 30 Gy: 33; 28.5 Gy: 33) have occurred. CONCLUSION: At 10 years, there was no significant difference in NTE rates after 28.5 Gy/5 fr compared with 50 Gy/25 fr, but NTE were higher after 30 Gy/5 fr. Results confirm the published 3-year findings that a once-weekly 5-fr schedule of whole-breast radiotherapy can be identified that appears to be radiobiologically comparable for NTE to a conventionally fractionated regimen.

The impact of intra-fractional bladder filling on "Plan of the day" adaptive bladder radiotherapy.

A retrospective audit on the "Plan of the day" (POD) selection and intra-fractional bladder fillings were carried out on twenty adaptive bladder radiotherapy patients at a single institution. Treatment time, differences in bladder volume and displacement of outer bladder wall expansion over the treatment fraction were analysed. Average treatment time was 8.9 min. The mean percentage difference in bladder volume pre and post treatment was 13.7%, resulting in expansion of the bladder predominately in the superior and anterior directions. This audit confirmed that the institution's POD process sufficed without being significantly affected by the intra-fractional bladder filings.