AMAZONE: Prevention of Persistent Pain after Breast Cancer Treatment by web-based Cognitive Behavioural Therapy

Profound advances in treatment of breast cancer have led to decreased mortality
and increased five-
year survival rates. However surviving breast cancer does not necessarily mean
complete
recovery to a premorbid state of health. In the past decade it became clear
that cancer survivorship
comes with many somatic and psychological problems requiring continuing medical
care. Among
these, persisting pain after breast cancer treatment (PPBCT) is probably the
most invalidating,
increasing survivor*s symptom burden and negatively affecting mood, sleep,
daily activities and
quality of life In the Netherlands 12.000 women per year are diagnosed with
breast cancer. With
an average prevalence of PPBCT of 30%. This means that yearly around 3600 new
women develop persisting pain in the operated area. PPBCT has relevant impact
on their quality of
life and capacity to resume their premorbid life and state of functioning.
Considering that this
number is augmenting, breast cancer survivorship leads to personal suffering
and enormous health
care and socio-economic costs.
Once chronic, PPBCT is difficult to treat and requires a complex
multidisciplinary approach. Studies
have been performed to prevent PPBCT by modifying somatic risk factors:
reducing the extent of
surgery, optimizing radiation dose and -field, and aggressive treatment of
perioperative pain. Except
for avoiding axillary node clearance, postoperative ketamine and perioperative
venlafaxine, none of
them convincingly reduced prevalence or severity of chronic pain.
Psychological risk factors for PPBCT have been identified in multiple studies
with the most
consistent evidence for the role of anxiety and pain catastrophizing. Anxiety
and other
psychological distress factors are hypothesized to lead to central
sensitization and increased
nociceptive signal transmission and thereby intensify and prolong pain.
Therefore, modifying
these psychological risk factors around the time of surgery may be a promising
approach to reduce
PPBCT. This study examines the preventive effect of a pre- and postoperative
psychological intervention (cognitive behavioral therapy; CBT) on the
development of PPBCT,
specifically targeting patients with high levels of anxiety and/or pain
catastrophizing. An RCT is
conducted comparing peri-operative CBT with a control intervention consisting
of education.
It is hypothesized that peri-operative CBT will reduce prevalence of PPBCT in
high anxious, high catastrophizing patients
by 50% at the 6 and 12 months follow-up assessment. Moreover, we hypothesize
that high anxious/catastrophizing patients show pathological central
sensitization.

The primary aim of the project is to find evidence that perioperative reduction
of anxiety and pain
catastrophizing by means of internet-based cognitive behavioral therapy (i-CBT)
reduces the
prevalence and intensity of PPBCT and post-treatment symptom load.
The secondary aim is to examine the hypothesis that central sensitization and
increased nociceptive
signal transmission underlies the influence of anxiety/pain catastrophizing on
persistent pain, and
that i-CBT affects this diathesis.

The study is conducted in three specialized centers for the treatment of breast
cancer. Patients are asked to participate in the study while preparing for
breast cancer surgery. Before surgery, questionnaires screen for the presence
of pain, catastrophizing and anxiety (in general and specifically for surgery
or cancer recurrence). Patients who score above average on one of these aspects
are randomized to one of two treatments: CBT or a control treatment. Both
treatments are offered via the internet and consist of one preoperative and
four postoperative sessions. An equally large group of women who score below
average for anxiety, undergo the same measurements, but do not receive an
intervention.
The effects of the interventions on pain, functioning and quality of life are
measured using online questionnaires taken before surgery and 2, 6 and 12
months after surgery. Acute post-operative pain will be assessed with a diary
during the first seven postoperative days. The patient's sensitivity to painful
stimuli is assessed using quantitative sensory testing (QST) and conditioned
pain modulation performed before surgery and 7 days and 6 months after
surgery.

The internet CBT intervention will consist of one preoperative session to
decrease anxious apprehension of the upcoming procedure and to provide patients
with tools to handle acute post-operative pain. Four sessions are given in the
weeks following surgery, to be scheduled at patients* own pace, but preferably
in the first 6 weeks. The ingredients of the intervention are based on existing
protocols for decreasing preoperative anxiety and pain catastrophizing and fear
of cancer recurrence and are developed in consultation with an experienced
psycho-oncologist and patient representatives.

All sessions consist of an information/education part, skills training and
homework assignments. After enrollment and before entering the first online
session, patients meet with their therapist (via secured platform) who explains
the aims of the program and addresses individual concerns.
Session 1 (preoperatively) is devoted to reducing pain catastrophizing and
surgical fear and building skills to cope with acute postoperative pain. It
consists of pain education, identification of dysfunctional pain cognitions,
cognitive restructuring and progressive muscle relaxation (PMR). Session 2 is
devoted to coping with pain and symptoms related to treatment. It consists of
identification of dysfunctional cognitions; cognitive restructuring; pleasant
activity scheduling; PRM and guided imagery. Session 3 is devoted to reducing
fear of recurrence. It consists of learning to distinguish between benign
symptoms and symptoms needing attention; identification of FCR-triggers and
coping with them, learning to control excessive worries and threat monitoring.
PRM and guided imagery are continued. Session 4 is devoted to life priorities
and goal setting. It consist of identification of one*s life priorities and
setting realistic goals for the future, increasing physical activity and
pleasant activity scheduling. PRM and guided imagery are continued. Session 5
is devoted to rehearsal, continued practice and maintenance. Contact (via
secured online platform) with a onco-psychologist is scheduled before session
1, during session 3 and after session5.

The control interventions consists of one preoperative internet-based
information session on what to expect during surgery and the post-surgical
period. After surgery, patients have access to four lessons related to healthy
living (diet, exercising, sleep, alcohol & smoking). The information will
partly be based on public sources such as Kanker.nl and digitized into an
attractive package. Before the first online session, patients have an
appointment with a team member to explain the aim of the program and address
concerns. After 3 and 6 weeks, patients are contacted to encourage them and to
ask if they have any questions.

The burden consists of participants having to invest time.
Completing the questionnaires takes 15-20 minutes per time point.
Participants randomized to the intervention conditions invest approximately 60
minutes per session (5 session) and approximately 10-15 minutes per meeting
with the psychologist (3 times).
In addition, participants who give separate permission for this, will receive 3
assessments of quantitative sensory testing. This takes about 60 minutes per
session and requires good collaboration and concentration of the patients while
different mechanical and thermal stimuli are applied to the thoracic wall,
neck, hand and knees. Some of the stimuli might cause a certain extent of
discomfort but are not harmful or extremely painful.