Burden of cancer trial participation: A qualitative sub-study of the INTERIM feasibility RCT

Objective A qualitative sub-study was carried out within a larger phase II feasibility trial, to identify and describe the burden experienced by advanced melanoma patients participating in a clinical trial and the factors affecting their capacity to cope with the burden. Methods Semi-structured interviews were conducted with fourteen patients with advanced melanoma recruited from National Health Service hospitals in the United Kingdom. Qualitative analysis was undertaken using a framework analysis approach. Normalisation process theory was applied to the concept of research participation burden in order to interpret and categorise findings. Results Burdens of participation were identified as arising from making sense of the trial and treatment; arranging transport, appointment and prescriptions; enacting management strategies and enduring side effects; reflecting on trial documents and treatment efficacy, and emotional and mental effects of randomisation and treatment side effects. Factors reported as influencing capacity include personal attributes and skills, physical and cognitive abilities and support network. Discussion This is the first study to highlight the substantial burden faced by patients with advanced melanoma in a clinical trial and factors that may lessen or worsen the burden. Consideration of identified burdens during trial design and execution will reduce the burden experienced by research participants.

hENT1 Predicts Benefit from Gemcitabine in Pancreatic Cancer but Only with Low CDA mRNA

Gemcitabine or 5-fluorouracil (5-FU) based treatments can be selected for pancreatic cancer. Equilibrative nucleoside transporter 1 (hENT1) predicts adjuvant gemcitabine treatment benefit over 5-FU. Cytidine deaminase (CDA), inside or outside of the cancer cell, will deaminate gemcitabine, altering transporter affinity. ESPAC-3(v2) was a pancreatic cancer trial comparing adjuvant gemcitabine and 5-FU. Tissue microarray sections underwent in situ hybridization and immunohistochemistry. Analysis of both CDA and hENT1 was possible with 277 patients. The transcript did not correlate with protein levels for either marker. High hENT1 protein was prognostic with gemcitabine; median overall survival was 26.0 v 16.8 months (p = 0.006). Low CDA transcript was prognostic regardless of arm; 24.8 v 21.2 months with gemcitabine (p = 0.02) and 26.4 v 14.6 months with 5-FU (p = 0.02). Patients with low hENT1 protein did better with 5-FU, but only if the CDA transcript was low (median survival of 5-FU v gemcitabine; 29.3 v 18.3 months, compared with 14.2 v 14.6 with high CDA). CDA mRNA is an independent prognostic biomarker. When added to hENT1 protein status, it may also provide treatment-specific predictive information and, within the frame of a personalized treatment strategy, guide to either gemcitabine or 5FU for the individual patient.

Total Laparoscopic Nerve-Sparing Radical Hysterectomy Using the No-look No-touch Technique

Radical hysterectomy is a standard operation for patients with early-stage cervical cancer. Over the recent decades, laparoscopic radical hysterectomy has been considered an alternative treatment. In 2018, the results of the laparoscopic approach to cervical cancer trial suggested that women with early-stage cervical cancer who underwent minimally invasive surgery for radical hysterectomy had poorer prognosis than those who underwent open surgery. This finding was unexpected, and direct evidence supporting poor prognosis related to minimally invasive radical hysterectomy was not available because the trial was not designed to evaluate the cause of the inferior outcomes. Tumor spillage caused by surgeon-related factors, including squeezing of the uterine cervix and tumor exposure to circulating CO2 gas, is considered to be associated with the poor prognosis of patients who underwent minimally invasive radical hysterectomy. We believe that protective maneuver to avoid tumor spillage is the key to improve oncologic outcomes of cervical cancer. Here, we present a procedure of total laparoscopic nerve-sparing radical hysterectomy for early-stage cervical cancer in which techniques, such as the “no-look no-touch technique,” were used to prevent tumor spillage.

Testing approaches to sharing trial results with participants: The Show RESPECT cluster randomised, factorial, mixed methods trial

Background Sharing trial results with participants is an ethical imperative but often does not happen. We tested an Enhanced Webpage versus a Basic Webpage, Mailed Printed Summary versus no Mailed Printed Summary, and Email List Invitation versus no Email List Invitation to see which approach resulted in the highest patient satisfaction with how the results were communicated. Methods and findings We carried out a cluster randomised, 2 by 2 by 2 factorial, nonblinded study within a trial, with semistructured qualitative interviews with some patients (ISRCTN96189403). Each cluster was a UK hospital participating in the ICON8 ovarian cancer trial. Interventions were shared with 384 ICON8 participants who were alive and considered well enough to be contacted, at 43 hospitals. Hospitals were allocated to share results with participants through one of the 8 intervention combinations based on random permutation within blocks of 8, stratified by number of participants. All interventions contained a written plain English summary of the results. The Enhanced Webpage also contained a short video. Both the Enhanced Webpage and Email contained links to further information and support. The Mailed Printed Summary was opt-out. Follow-up questionnaires were sent 1 month after patients had been offered the interventions. Patients’ reported satisfaction was measured using a 5-point scale, analysed by ordinal logistic regression estimating main effects for all 3 interventions, with random effects for site, restricted to those who reported receiving the results and assuming no interaction. Data collection took place in 2018 to 2019. Questionnaires were sent to 275/384 randomly selected participants and returned by 180: 90/142 allocated Basic Webpage, 90/133 Enhanced Webpage; 91/141 no Mailed Printed Summary, 89/134 Mailed Printed Summary; 82/129 no Email List Invitation, 98/146 Email List Invitation. About 3 patients opted out of receiving the Mailed Printed Summary; no patients signed up to the email list. Patients’ satisfaction was greater at sites allocated the Mailed Printed Summary, where 65/81 (80%) were quite or very satisfied compared to sites with no Mailed Printed Summary 39/64(61%), ordinal odds ratio (OR) = 3.15 (1.66 to 5.98, p < 0.001). We found no effect on patient satisfaction from the Enhanced Webpage, OR = 1.47 (0.78 to 2.76, p = 0.235) or Email List Invitation, OR = 1.38 (0.72 to 2.63, p = 0.327). Interviewees described the results as interesting, important, and disappointing (the ICON8 trial found no benefit). Finding out the results made some feel their trial participation had been more worthwhile. Regardless of allocated group, patients who received results generally reported that the information was easy to understand and find, were glad and did not regret finding out the results. The main limitation of our study is the 65% response rate. Conclusions Nearly all respondents wanted to know the results and were glad to receive them. Adding an opt-out Mailed Printed Summary alongside a webpage yielded the highest reported satisfaction. This study provides evidence on how to share results with other similar trial populations. Further research is needed to look at different results scenarios and patient populations. Trial registration ISRCTN: ISRCTN96189403.