C.L. Ferguson

Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology–RTOG 1203

Purpose NRG Oncology/RTOG 1203 was designed to compare patient-reported acute toxicity and health-related quality of life during treatment with standard pelvic radiation or intensity-modulated radiation therapy (IMRT) in women with cervical and endometrial cancer. Methods Patients were randomly assigned to standard four-field radiation therapy (RT) or IMRT radiation treatment. The primary end point was change in patient-reported acute GI toxicity from baseline to the end of RT, measured with the bowel domain of the Expanded Prostate Cancer Index Composite (EPIC). Secondary end points included change in patient-reported urinary toxicity, change in GI toxicity measured with the Patient-Reported Outcome Common Terminology Criteria for Adverse Events, and quality of life measured with the Trial Outcome Index. Results From 2012 to 2015, 289 patients were enrolled, of whom 278 were eligible. Between baseline and end of RT, the mean EPIC bowel score declined 23.6 points in the standard RT group and 18.6 points in the IMRT group ( P = .048), the mean EPIC urinary score declined 10.4 points in the standard RT group and 5.6 points in the IMRT group ( P = .03), and the mean Trial Outcome Index score declined 12.8 points in the standard RT group and 8.8 points in the IMRT group ( P = .06). At the end of RT, 51.9% of women who received standard RT and 33.7% who received IMRT reported frequent or almost constant diarrhea ( P = .01), and more patients who received standard RT were taking antidiarrheal medications four or more times daily (20.4% v 7.8%; P = .04). Conclusion Pelvic IMRT was associated with significantly less GI and urinary toxicity than standard RT from the patients perspective.

Thoracic radiation-induced pleural effusion and risk factors in patients with lung cancer

The risk factors and potential practice implications of radiation-induced pleural effusion (RIPE) are undefined. This study examined lung cancer patients treated with thoracic radiation therapy (TRT) having follow-up computed tomography (CT) or 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Increased volumes of pleural effusion after TRT without evidence of tumor progression was considered RIPE. Parameters of lung dose-volume histogram including percent volumes irradiated with 5-55 Gy (V5-V55) and mean lung dose (MLD) were analyzed by receiver operating characteristic analysis. Clinical and treatment-related risk factors were detected by univariate and multivariate analyses. 175 out of 806 patients receiving TRT with post-treatment imaging were included. 51 patients (24.9%) developed RIPE; 40 had symptomatic RIPE including chest pain (47.1%), cough (23.5%) and dyspnea (35.3%). Female (OR = 0.380, 95% CI: 0.156-0.926, p = 0.033) and Caucasian race (OR = 3.519, 95% CI: 1.327-9.336, p = 0.011) were significantly associated with lower risk of RIPE. Stage and concurrent chemotherapy had borderline significance (OR = 1.665, p = 0.069 and OR = 2.580, p = 0.080, respectively) for RIPE. Patients with RIPE had significantly higher whole lung V5-V40, V50 and MLD. V5 remained as a significant predictive factor for RIPE and symptomatic RIPE (p = 0.007 and 0.022) after adjusting for race, gender and histology. To include, the incidence of RIPE is notable. Whole lung V5 appeared to be the most significant independent risk factor for symptomatic RIPE.The risk factors and potential practice implications of radiation-induced pleural effusion (RIPE) are undefined. This study examined lung cancer patients treated with thoracic radiation therapy (TRT) having follow-up computed tomography (CT) or 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Increased volumes of pleural effusion after TRT without evidence of tumor progression was considered RIPE. Parameters of lung dose-volume histogram including percent volumes irradiated with 5-55 Gy (V5-V55) and mean lung dose (MLD) were analyzed by receiver operating characteristic analysis. Clinical and treatment-related risk factors were detected by univariate and multivariate analyses. 175 out of 806 patients receiving TRT with post-treatment imaging were included. 51 patients (24.9%) developed RIPE; 40 had symptomatic RIPE including chest pain (47.1%), cough (23.5%) and dyspnea (35.3%). Female (OR = 0.380, 95% CI: 0.156–0.926, p = 0.033) and Caucasian race (OR = 3.519, 95% CI: 1.327–9.336, p = 0.011) were significantly associated with lower risk of RIPE. Stage and concurrent chemotherapy had borderline significance (OR = 1.665, p = 0.069 and OR = 2.580, p = 0.080, respectively) for RIPE. Patients with RIPE had significantly higher whole lung V5-V40, V50 and MLD. V5 remained as a significant predictive factor for RIPE and symptomatic RIPE (p = 0.007 and 0.022) after adjusting for race, gender and histology. To include, the incidence of RIPE is notable. Whole lung V5 appeared to be the most significant independent risk factor for symptomatic RIPE.

The EAGLE study: improving the wellbeing of men by evaluating and addressing the gastrointestinal late effects of radical treatment for prostate cancer.

Citation for published version (APA): Rogers, A., Mackenzie, I., Rorie, D., & MacDonald, T. (2017). Successful recruitment to a large online randomised trial: the TIME study. In Trials: Meeting abstracts from the 4th International Clinical Trials Methodology Conference (ICTMC) and the 38th Annual Meeting of the Society for Clinical Trials (Supplement 1 ed., Vol. 18, pp. 222-223). [089] (Trials; Vol. 18, No. Suppl. 1). United Kingdom: BioMed Central. https://doi.org/10.1186/s13063-017-1902-yThe study will address variability in practice, defined in Standard Operating Procedures, that UK Clinical Trials Units (CTU) have in place for: i) defining, ii) classifying, and iii) reporting adverse events in non-CTIMPs. Compared to drug trials, adverse events in non-CTIMPs are not managed well. There is considerable inconsistency in reporting styles between trials of similar design and intervention type. To promote increased consistency, we will conduct a consensus exercise among non-CTIMP experts using a Delphi technique followed by a face-to-face meeting. This method adheres to the recommended sequence outlined by the international network for Enhancing the Quality and Transparency of Health Research (EQUATOR) for developing health research guidelines. A non-CTIMP expert is defined as: a CTU representative, a Chief Investigator or trial manager of non-CTIMPs with >3 trials experience in this role, or a senior member of the Health Research Authority’s Operations team or Ethics Committee. As such, the participants in the consensus exercises will also be the direct beneficiaries from the project maximising its pathway to impact. Following the face-to-face meeting — guidance and explanatory statements will be drafted. The guidance statement will focus on: • how adverse events should be defined in relation to the non-pharmacological intervention, • how CTU standard operating procedures should be designed to reflect the results of the Delphi exercise, • how adverse events should be classified following a judicious causal assessment, and • recommended reporting methods that will promote more effective meta-analyses of non-pharmacological interventions that provide a balanced benefit-harm evaluation. Following study completion, we will work with a selection of UK CTUs to evaluate the implementation of any agreed modifications to current practice.This is the final version of the article. Available from BioMed Central via the DOI in this record.Objective Multi-centre RCT designs provide robust evidence of therapeutic effect of health interventions. However participating centres often differ in how well they conduct the trial and the number of patients successfully recruited. This paper describes barriers different research teams encountered when conducting a complex RCT comparing a surgical procedure with physiotherapy, and the actions taken by the trial management group to overcome obstacles that were hindering recruitment. Methods We conducted 22 interviews with principal investigators and research associates at 14 sites involved in the delivery of a surgical RCT that compared hip arthroscopy and physiotherapy for hip pain. Interview transcripts were analysed thematically and case study approaches were utilised to present results to the trial management group. Results Research teams reported difficulties related to logistics (e.g. Room space); motivation (e.g. PI reluctant to approach patients); and skill (e.g. Lack of knowledge about the treatment arms). Similar Issues were shared by sites that recruited to target and those that did not, however there were differences in the team ’ s response to challenges. Whilst on-target sites found local solutions to issues or support through their research infrastructure or the trial TMG, off-target sites usually did not show proactivity. Site profiles were created and action plans designed based on aspects that were particular to the individual sites. These plans were implemented in collaboration with site teams. Conclusions This qualitative study added to the growing evidence of how aspects of team functioning are important for recruitment to complex RCTs. Trial Management Groups can help research teams identify and ad- dress issues, and therefore contributing to a sense of ownership by the research team. Empowering research teams to find solutions at local level is essential to conduct multi-centre RCTs successfully.

Late effects of pelvic radiation treatment (EAGLE study).

159 Background: Radiotherapy treatment for prostate cancer can cause severe long -term bowel problems, including limiting travel, work or socialising. Around half of patients suffer from late effects, appearing more than six months after radiotherapy. These symptoms often remain unmonitored in follow up care, despite the existence of effective treatment if referred to gastroenterology departments. This study focuses on the early identification and treatment of neglected late effect symptoms. METHODS Novel healthcare interventions are often difficult to embed in local clinical settings. Implementation research methodology will be used to evaluate experiences of a multi-component intervention aimed at prompting referrals to an enhanced gastroenterology service, making real time adjustments as needed, with the ultimate aim of successfully embedding the intervention into practice across the UK. The intervention, introduced in three UK centres, comprises a brief, standardised clinical assessment of relevant symptoms and rapid referral to a gastroenterological service, with staff trained to use a validated investigation and treatment algorithm. Evaluation of the intervention and its acceptability within local practices will be conducted using longitudinal mixed methods research. All prostate cancer patients attending follow up clinics, meeting the eligibility criteria will be invited to be screened (n = 300) and offered a referral to gastroenterology if appropriate. A cost effectiveness analysis of health-related quality of life and resource utilisation data will be undertaken and contrasts made between participants and a comparison group. RESULTS Interim results will focus on interview data from healthcare professionals and how they are working locally to embed practice, sharing learning points with other locations whilst working towards a sustainable service. CONCLUSIONS This study evaluates the effectiveness of an enhanced assessment and treatment service spanning oncology and gastroenterology services in improving the outcome of men with prostate cancer after radiotherapy. Successful implementation will act as examples of best practice for a network of centres of excellence in this area.