Gender Neutral
Type Module
Testing Phase IV - in development
Principal investigator(s)
Anne-Sophie Darlington
School of Health Sciences, University of Southampton
Southampton, United Kingdom
, Colin Johnson
Cancer Sciences, University of Southampton
Southampton, United Kingdom
, Vassilios Vassiliou
Bank of Cyprus Oncology Centre
Limassol, Cyprus
Study coordinator(s)
Samantha Sodergren
Faculty of Health Sciences, University of Southampton
Southampton, United Kingdom
, Amy Din
Faculty of Health Sciences, University of Southampton
Southampton, United Kingdom

Project summary

Anal carcinoma is an uncommon malignancy accounting for 2% of all gastrointestinal malignancies and 10% of all anorectal malignancies, but with increasing incidence over the past 25 years and higher incidence seen in women.  The current standard of care of patients with non-metastatic squamous cell cancers of the anal canal is intensive concurrent chemoradiotherapy which allows for sphincter preservation and has impressive treatment outcomes (survival rate of 65-70% and complete pathological response rate of about 90%).  However, this treatment has acute and chronic toxicities.  Potential complications include radiation enteritis, diarrhoea, proctitis, skin desquamation, strictures, stenosis, sexual dysfunction, dyspareunia, pelvic fractures, induced menopause, lymphedema, urgency and frequency of defecation, stool incontinence, and urinary tract dysfunction. There is a paucity of research looking at the impact of anal cancer and its treatment on quality of life (QoL) and as there is no anal cancer specific questionnaire, the studies that have been carried out have relied on measures designed for different tumour types (such as colorectal) thus they fail to capture the specific acute and long term complications experienced by anal cancer patients.

The development of the anal cancer module follows the EORTC QLG guidelines and is split into phases. So far we have completed the first three phases:

Phase I  Generation of issues

In order to generate a list of QoL issues facing anal cancer patients treated with chemoradiotherapy, we looked at the literature, and interviewed patients and health care professionals (HCPs).  Our systematic review of the literature identified 11 studies which used a formal assessment of quality of life.  Recruitment of 43 patients took place from 7 centres across 5 countries (UK:  Southampton and London; Cyprus:  Nicosia; Canada:  Ottawa and Toronto; Poland:  Krakow; Germany:  Halle).   A list of 134 issues was then reviewed by 34 health care professionals and a separate group of 10 patients from Southampton, UK.

Phase II Provisional Anal Cancer Quality of Life Module

Analysis of Phase I data resulted in 65 issues, which were then formulated into questions using the EORTC QLG item library and modules in development at that time (vulva and cachexia).  For 23 issues there was no suitable match and therefore new questions were created.  The EORTC QLG Translation Department prepared the following versions of the questionnaire:  English, Greek, Polish, German, French, Italian and Norwegian.

Phase III Pilot testing the Provisional Anal Cancer Quality of Life Questionnaire

The provisional 65-item questionnaire was pilot tested with a new, larger (n=100) cohort of patients recruited amongst the Phase I sites as well additional sites (Greece, Italy and Norway). Patients completed the anal cancer questionnaire and the core EORTC Questionnaire (EORTC QLQ-C30) followed by a debrief interview asking about the relevance and importance of questions, whether any questions were upsetting or confusing and whether there were any important omissions.  The questionnaire was subsequently refined to a 27 item questionnaire EORTC QLQ-ANL27 which has been approved by the EORTC QLG.  The EORTC QLQ-ANL27 includes four HRQoL domains: pain, bowel, sexual and stoma care problems and five single item (frequent urination, keeping clean, proximity to toilet, lower limb oedema, planning activities).

The EORTC QLQ-ANL27 is used alongside the EORTC QLQ-C30 as the patient reported outcome assessment component of the Personalising Anal Cancer Radiotherapy Dose (PLATO) trial led by Professor David Sebag-Montefiore, in Leeds, UK.

Current status:  Phase IV

Phase IV international validation of the EORTC QLQ-ANL27 is now underway with a target recruitment of 375 patients which we hope to achieve by April 2019. As part of this phase, patients will be invited to complete the EORTC QLQ-ANL27 alongside the EORTC QLQ-C30 on one or two occasions which will allow us to test the performance of the measure including its responsiveness to change and test-retest reliability.  We will also be able to confirm the subscale structure of the EORTC QLQ-ANL27.

Achievements

To date, we have developed a provisional HRQoL measure specific to the concerns of anal cancer patients treated with chemoradiotherapy – the EORTC QLQ-ANL27. The EORTC QLQ-ANL27 is the product of three phases of work which included a systematic literature review, patient and health care professional (HCP) interviews (53 patients and 34 HCPs) and reviews as well as preliminary testing of the pilot 65-item questionnaire with 100 patients.  The EORTC QLQ-ANL27 covers 4 domains of HRQOL concern: pain, bowel, sexual and stoma care problems and five single item (frequent urination, keeping clean, proximity to toilet, lower limb oedema, planning activities). We are currently validating the EORTC QLQ-ANL27 in a larger group of patients (target of 375 participants) recruited from International centres.  This current phase of research will confirm whether the EORTC QLQ-ANL27 is a psychometrically sound instrument in terms of responsiveness to change and consistency and we will verify the scale structure.

Future plans

We anticipate completing data recruitment in April 2019 and will be in a position to submit a Phase IV report to the EORTC QLG in September 2019.

For patients

Anal cancer is rare and is currently treated with chemotherapy and radiotherapy (CRT) in combination. While treatment outcomes are promising, their side effects often have long lasting effects on health-related quality of life (HRQoL). There is little research into these side-effects and there is no anal cancer specific questionnaire to assess HRQoL. In order to develop a HRQoL questionnaire specifically for anal cancer patients, we reviewed the literature on anal cancer and interviewed patients and healthcare professionals (HCPs) from 8 countries. We then developed a list of 197 issues, which was refined into a 65-item questionnaire. The final questionnaire, the “EORTC QLQ-ANL27” includes 27 questions covering pain, bowel, sexual and stoma care problems which may help the management of side-effects and provision of psychological support. Asking patients to complete this questionnaire may help to understand where they need support.

Publications

Sodergren SC, Johnson CD, Gilbert A, Tomasewski KA, Chu W, Chung HT, Dennis K, Desideri I, Glynne-Jones R, Guren MG, Kardamakis D, Nugent K, Schmidt H, Sebag-Montefiore D, Vassiliou V. on behalf of the EORTC Quality of Life Group. Phase I–III development of the EORTC QLQ-ANL27, a health-related quality of life questionnaire for anal cancer. Radiotherapy and Oncology, 2018, 126, (2) 222–228