Research Article :
Marie-Rose Dwek, Lorna Rixon, Alice Simon, Catherine Hurt and Stanton Newman Results: From 1 April
2014 to 1 December 2014, 42 eligible participants were invited to take part in
the trial. Of the 17 that completed pre-chemotherapy assessments, only 1 withdrew
at follow-up due to reasons of ill health from disease recurrence. All
participants completed the entire battery and indicated that they found the
trial acceptable. Research suggests that
chemotherapy may be related to a decline in cognitive
functions such as memory and attention in some solid tumour
cancer patients [1-4]. However, the presence, extent and
course of any cognitive decline and whether or notit causes observable
difficulties for patients remain unclear. The majority of research studies to
date have explored cognitive function in cancer patients after treatment has
been completed [5]. Few studies have measured patients cognitive function prior
to the commencement of chemotherapy treatment and hence these studies do not
have any baseline. Measuring cognitive function both before and after
chemotherapy would make it possible to identify changes occurring during treatment
and the duration of such treatment related changes. An additional limitation of
existing studies is that they have often lacked a comparison group (e.g. cancer
patients who have not required chemotherapy) against which to compare cognitive
function scores. Furthermore, the majority of cognitive research to date has
focussed on female breast
cancer patients. This has precluded an exploration of gender differences in
relation to cognitive decline. This study examines the feasibility of a
protocol designed to examine the nature and extent of chemotherapy related
cognitive changes in colorectal cancer (“CRC”) patients (the “Protocol”) [6].
Given the proposed scale of the study, it was considered appropriate to first
conduct a feasibility trial (the “Trial”). It is good practice and important
for research to carry out this type of feasibility trial prior to a full study
[7]. The Trial would determine the resources required, whether the Protocol
could be implemented as designed, or whether any alterations were necessary. Bowen et al [8] suggested eight
general areas of focus that may be addressed by feasibility studies for proposed
interventions. This was narrowed to four areas, as the Trial did not involve an
intervention. (See Table 1, which defines how the areas of focus correspond to
the Trial objectives). The primary
objectives of this Trial were to evaluate: Recruitment
procedures: In
order to assess the maximum number of eligible participants, the most efficient
procedures for recruitment were examined so as to establish and confirm the: a) Extent to which the suggested
recruitment procedures could be carried out as proposed b) Similarities/differences in
recruitment procedures between the three collaborating London based NHS Trusts
(the Trusts) c) Extent to which the clinical
teams were supportive of the Trial d) Ease of identifying eligible
participants e) Number of eligible
participants per Trust. Participant
numbers: A
critical issue was to examine the patient flow as determined by the consent
rate of eligible participants entering this Trial in order to [9-11]. a) Determine the time necessary to recruit a
sufficient sample b) Make projections of the
funding and resources needed to execute an appropriately powered multi-site
study c) Assess the suitability of
inclusion/exclusion criteria. Methodology/testing
of Data Collection Procedures and Assessments: The piloting and
assessing acceptability of the proposed technique of data collection [11]
according to the Protocol, was
important, as each participant was required to undergo a series of neuropsychological
assessments and questionnaires (the “Battery”). Attrition rates:
Similar
research in breast cancer treatment suggests that attrition rates in
longitudinal cohort studies range from 10% to 33% [12-15]. The extent to which
these data would be generalisable to the proposed population who differed in age,
gender, cancer type and course of treatment needed to be determined. Ethical approval was obtained
from the NHS Health Research Authority – NRES Committee South-West Cornwall
& Plymouth in August 2013. As part of the approval process it was also
necessary to obtain a patients perspective and view of the proposed Trial. Therefore
prior to commencing the Trial an advertisement was posted on the Macmillans
Cancer Support online community noticeboard
(http://community.macmillan.org.uk/volunteering/ noticeboard/default.aspx) and
also on Beating Bowel Cancers patient forum
(http://www.beatingbowelcancer.org/forum), asking bowel cancer patients for
their general opinions and thoughts on the Trial. The feedback received was
positive. The study was considered to be “worthwhile”. In accordance with the Protocol,
a longitudinal cohort study was implemented between 1 April 2014 and 1 December
2014 inclusive (the Trial Period). Data was collected at: • T1” post-surgery and prior to chemotherapy
treatment • T2” twelve to fourteen weeks
after first scheduled chemotherapy treatment or 3 months post surgery (as
appropriate) • T3” three months after last
scheduled chemotherapy
treatment or approximately 6 months after T2 (as appropriate). Participants During the Trial Period, a
consecutive sample of patients between the ages of 18 and 65, diagnosed with
resectable CRC under the care of the CRC team were invited to participate. Eligibility required patients to: a) Have undergone colorectal
surgery b) Not have distant metastases;
and c) Require adjuvant chemotherapy treatment or no postsurgery
treatment at all. Patients with prior exposure to
chemotherapy and those with significant psychiatric
or medical comorbidities, which might affect ability to participate in the
Trail, were excluded. Patients could not enter the Trial if they were unable to
read and speak English. Measures The measures used are detailed in
the Protocol [6]. Trial sample
size Extrapolating from the Protocols
power calculation and assuming a total sample size of 156 participants (78 per
group) to be recruited over 18 months, an average of eight to ten patients per calendar
month would need to be consented into the Trial. Potential participants were
identified at the weekly CRC multidisciplinary team (MDT) meetings held by each
Trust. Proposed recruitment procedures were as follows: • At the participants
post-surgery follow-up appointment, typically three to six weeks after surgery
(OPA), a member of the clinical team would introduce the researcher to the
patient. • The researcher would then
provide the patient with written information about the Trial and answer
questions raised. • The patient would be asked if
they would be willing to be contacted by telephone within a few days to discuss
participation in the Trial. Patients who agreed to participate were then given
an appointment to meet with the researcher either at the hospital or at home. Those
patients who did not wish to participate after reviewing the information sheets
were not contacted again. T1 assessments were planned to take place one to two weeks
after the OPA and prior to the patients first scheduled chemotherapy
appointment or at a parallel point in time for the surgery-only group. Eligible
participants were to be consented into the Trial immediately prior to T1. The
assessments for T1 were expected to take each participant approximately 2 hours
and 30 minutes to complete. At the end of T1 participants were advised that
they would be contacted again via telephone within approximately 10 to 12 weeks
to arrange the meeting for T2. T2 would be scheduled for between 12 and 14
weeks after T1 or between cycle 6 and cycle 7 in the case of the chemotherapy
treatment group and at a parallel point in time for the surgery only group. The
same process would be utilised for T3, with assessments carried out at
participants homes at approximately 3 months after the final scheduled
chemotherapy treatment, and at a similar point in time for the surgery-only
participants. Based on the sample size calculation set out in the Protocol, the
attrition rate could not exceed 22%. Recruitment
procedures The Trial indicated that
procedures were quite similar at each Trust. At all Trusts the surgery-only
follow-up appointments were more difficult to determine than the chemotherapy
patients. Participant
numbers Recruiting from three Trusts (six
hospital sites), attending all MDTs, surgical and chemotherapy clinics whilst
also carrying out all assessments exceeded the single researchers capacity; indicating
that recruitment would require additional staff. The surgery only control group
proved more complex to recruit, as there were multiple surgeons at each
hospital site making it difficult to identify all follow up OPAs. In addition
eligible surgery
only participants approached by the researcher often refused participation as
they asserted that they had completed treatment. Forty-two CRC patients across
3 Trusts were invited to participate during the Trial Period, twenty-three
agreed and were consented; however five changed their minds prior to completing
T1. At the end of the Trial Period eighteen had completed T1 and eight T2.
Seventeen of the eighteen remained in the Trial after the Trial Period and
completed T2. One patient withdrew after T1 due to the appearance of a new
cancer lesion. The sample at T1 was made up from 38.8% males and 61.2% females
with a mean age of 59.7% years. Fourteen of the eighteen participants (77.8%)
were in the chemotherapy group. However, one participant was advised to start
chemotherapy treatment several weeks after completing T1 and another that
started in the chemotherapy
group stopped treatment after three cycles but continued in the Trial. The rate
of recruitment was approximately three per month once the recruitment
procedures and working practices were established. This indicated that
significantly more research capacity and sites were required as it would take
approximately four years to recruit the 156 participants required with the
current resource. Inclusion/exclusion
criteria Eligible participants were lower
in number than expected in part due to the inclusion/exclusion criteria, age
and also competing trials. Following ethics approval the age criterion was
altered to have no upper age limit to increase recruitment. Methodology/Testing
of data collection procedures and assessments All participants completed the full
Battery. Consequently the administration of the Battery was deemed appropriate.
A suitable testing environment
was achieved by administering the Battery in a quiet space both at the
hospitals and participants homes. At the completion of T1, participants were
asked how they felt about the assessments. The comments made suggested that participants
in both groups found the design, methods and procedures employed in the Trial
appropriate. ID 1: “this was very enjoyable” ID 14: “It took my mind off
things, I enjoyed doing it” Attrition rates During the Trial Period,
attrition at T2 was very low with only 1 participant withdrawing due to ill
health. All participants who completed T1 expressed a desire to continue in the
Trial. Continued participation in the Trial would suggest that the proposed
multi-site study is worthwhile. The Trial provided evidence that
the Protocol is feasible subject to increasing the number of researchers and
collaborating sites both to improve recruitment rates and to prevent clashes
with assessments. One possible solution to improving the rate of recruitment
was implemented during the Trial Period, by removing the upper age limit for
eligible participants. This has since made a difference in number of consented
participants. The number of patients consenting to the Trial and a very low
attrition rate suggests that many CRC patients are willing to participate and
that the Battery is feasible and well tolerated by patients. Another strength
of the proposed Protocol evidenced during the Trial was the acceptability of
the multi-site study to clinical teams demonstrated by requests of
collaboration from two additional London based NHS Trusts. In addition, the
Trial provides valuable information to other neuropsychologists interested in
the cognitive effect of chemotherapy
treatments in the form of a realistic plan. It also makes clear the
requirement for sufficient funding and resources. This could in turn allow for a
large multi-institutional study across several English speaking cities and/or
countries. All institutions could administer the same neuropsychological
battery to a very large number of solid tumour cancer patients and pool all
data as suggested by the International Cognition and Cancer
Task Force [4]. One potential limitation of the proposed study however, is that
the majority of patients had never heard of chemotherapy related cognitive
changes, which may cause concern and/or priming effects. However, in the event
that priming does occur it will do so in both the chemotherapy group and the
surgery only group, so useful comparisons between the groups of any observed
objective changes may still be made. In addition, any possible priming effects will
not prohibit the researchers from being able to examine the impact of
chemotherapy related subjective cognitive changes on the individuals quality of
life. Sponsors City University London PhD
studentship. Funded Marie-Rose Dweks PhD. Post script:
Funding from Barts Charity was subsequently awarded to City University London
in order to run an extended study and appoint further researchers. Grant
Number: 477/2313. 1. Collins B,
Mackenzie J, Stewart A, Bielajew C, Verma S. Cognitive effects of chemotherapy
in post-menopausal breast cancer patients 1 year after treatment (2009)
Psycho-Oncology 18: 134-143. *Corresponding author:
Stanton Newman, School of Health Sciences,
City University London, 10 Northampton Square,
London, Tel: +44 (0)207 040 5829,
Fax: +44 (0) 207 040 0875
E-mail: Stanton.Newman.1@city.ac.uk
Cancer, neuropsychological,chemotherapy treatments, surgery, colorectal surgery, breast cancer
Examining Chemotherapy-Related Cognitive Changes in Colorectal Cancer Patients: A Feasibility Trial
Abstract
Introduction: Research suggests that chemotherapy may be related to decline in
patients’ cognitive functions.
Objectives: To assess the feasibility and acceptability of a multi-site study designed
to examine the nature and extent of chemotherapy-related cognitive changes in
colorectal cancer patients.
Method: Data was
collected over 8 months using objective and self-reported measures of cognitive
functioning and self-reported quality of life, fatigue and mood questionnaires.
The assessment battery was administered pre- and mid-chemotherapy treatment to a consecutive sample
of colorectal cancer patients across three London based NHS Trusts. Participants
included patients who had undergone colorectal surgery and were scheduled to
have adjuvant chemotherapy treatment, or no further cancer treatment.
Main outcome
measures: Recruitment
procedures, rate of recruitment, suitability of exclusion/inclusion criteria,
acceptability of data collection procedures and the battery, and attrition
rates.
Conclusions:
What went wrong: Strained
researcher resources; loss of eligible participants to competing studies,
restrictive upper age limit.
Possible
solutions: Removal
of upper age limit, an increased dedicated research team to increase rate of
recruitment. The large multi-site study is
feasible with suggested amendments and is acceptable to patients and medical
teams. Acceptability of trial to medical teams is further evidenced by requests
of collaboration from two additional London based NHS Trusts.
Lessons learned:
This
feasibility trial provides evidence to other researchers designing similar
studies in this area of an acceptable design and the need for appropriate funding
for resources to recruit large enough consecutive samples of patients with
solid tumour cancers. Full-Text
Introduction
Objectives
Ethical Approval
Methods
Procedure
Results
Conclusions
References
2. Myers JS.
Chemotherapy-related cognitive impairment (2009) Clinical journal of oncology
nursing 13.
3. Weis J,
Poppelreuter M, Bartsch HH. Cognitive deficits as long-term side-effects of
adjuvant therapy in breast cancer patients:subjectivecomplaints
and objectiveneuropsychological test results (2009) Psycho-Oncology 18:
775-782.
4. Wefel JS, Lenzi R,
Theriault RL, Davis RN, Meyers CA. The cognitive sequelae of standard-dose
adjuvant chemotherapy in women with breast
carcinoma (2004) Cancer 100: 2292-2299.
5. Vardy J, Wefel JS,
Ahles T, Tannock IF, Schagen SB. Cancer and cancer-therapy related cognitive
dysfunction: an international perspective from the
Venice cognitive workshop (2008) Annals of Oncology 19:623-629.
6. Dwek, MR, Rixon L,
Simon A, Hurt C, Newman S. Examining the effects of adjuvant chemotherapy on
cognition and quality of life in colorectal cancer patients: study protocol
(2015) BMC Psychology.
7. Arain M, Campbell
MJ, Cooper C L, Lancaster GA. What is a pilot or feasibility study? A review of
current practice and editorial policy (2010) BMC Medical Research Methodology 10:
67.
8. Bowen DJ, Kreuter M, Spring B, Cofta-Woerpel L, Linnan L, et al. How we
design feasibility studies (2009) American journal of preventive medicine 36:
452-457.
9. Ross-McGill H,
Hewison J, Hirst J, Dowswell T, Holt A, et al. Antenatal home blood pressure
monitoring: a pilot randomised controlled trial (2000) BJOG: An International
Journal of Obstetrics & Gynaecology 107: 217-221
10. Burrows RF, Gan
ET, Gallus AS, Wallace EM, Burrows EA. A randomised double-blind placebo
controlled trial of low molecular weight heparin as
prophylaxis in preventing venous thrombolic events after caesarean section: a
pilot study (2001) BJOG: An International Journal
of Obstetrics & Gynaecology 108: 835-839.
11. Carfoot S,
Dickson R, Williamson PR. Breastfeeding: The effects of skin-to-skin care trial
(BEST), pilot study. In Celebrating Health Research: the Annual R & D
Conference (2002) North West Regional Health Authority, Manchester.
12. Hurria A, Rosen
C, Hudis C, Zuckerman E, Panageas KS, et al. Cognitive function of older
patients receiving adjuvant chemotherapy for breast cancer: a pilot prospective
longitudinal study (2006) Journal of the American Geriatrics Society 54:
925-931.
13. Reid-Arndt SA,
Hsieh C, Perry MC. Neuropsychological functioning and quality of life during
the first year after completing chemotherapy for breast cancer (2010)
Psycho-Oncology 19: 535-544.
14. Vearncombe KJ,
Rolfe M, Wright M, Pachana NA, Andrew B, et al., Predictors of cognitive
decline after chemotherapy in breast cancer patients (2009) Journal of the
International Neuropsychological Society 15: 951-962.
15. Wefel JS, Saleeba AK, Buzdar AU,
Meyers CA. Acute and late onset cognitive dysfunction associated with
chemotherapy in women with breast cancer (2010) Cancer 116: 3348-3356.
Citation: Dwek MR, Rixon L, Simon A, Hurt C,
Newman S (2016) Examining ChemotherapyRelated Cognitive Changes in Colorectal
Cancer Patients: A Feasibility Trial. COA 1: -6 Keywords
