Putting the patient at the center of care: personalized treatment for psychological symptoms and fatigue in cancer survivors

Approximately a third of patients with cancer experience clinically relevant
levels of psychological symptoms for which referral to a specialized health
care provider is indicated. Severe fatigue is also highly prevalent during and
after cancer treatment, in at least a quarter of patients. Both adversely
impact patients* functioning and quality of life, often co-occur, and can
strengthen each other.

Previous studies evaluated interventions for psychological symptoms and fatigue
in patients with cancer. The vast majority of these interventions are based on
a cognitive behavioral model which assumes that although cancer and cancer
treatment may trigger the symptoms, cognitive and behavioral factors
subsequently perpetuate and maintain these symptoms. Treatment targeting these
perpetuating and maintaining factors has been shown to decrease psychological
symptoms and fatigue and improve functioning in patients with cancer. However,
effect sizes of these psychological interventions are only small to medium,
uptake of interventions in clinical practice is rather low, and attrition rates
are relatively high.

Following the personalized medicine development, there has been a repeated call
for personalized psychological treatment. Tailoring treatment to specific
patient characteristics and needs is assumed to improve effectiveness of
interventions and increase engagement and adherence. There is, however, no
evidence that the tailoring of psychological interventions has added value to
standardized psychological care. Only one study made a direct comparison:
tailored internet-based cognitive behavior therapy (ICBT) versus non-tailored
ICBT in patients with major depression and comorbid psychological symptoms.
Although there was a trend in favor of tailored ICBT, effectiveness did not
significantly differ from non-tailored ICBT. No further evidence in favor of
either tailored therapy or non-tailored treatment exists.

Psychological treatment can be tailored in several ways and on various levels.
One level on which tailoring can take place, is treatment indication.
Currently, referral from patients with cancer to psychological care mainly
occurs based on availability of interventions or symptom level, rather than
need for care. This follows partly from national guidelines which recommend
screening for high symptom levels. Distress, even high distress, can be a sign
of normal adjustment, however, and patients may not be in need for professional
care. Fatigue can be severe, but not causing hindrance or disability. We and
others previously established this gap between distress and care needs. Symptom
level in itself does not provide information on whether the symptom is
burdensome or disabling, and whether patients have a need for care. It has been
repeatedly suggested that care needs should be evaluated and maybe even leading
the decision whether treatment is indicated.

Another level of tailoring concerns the focus and content of treatment.
Currently, psychological treatment is aimed at factors that are generally known
to maintain symptoms, such as inactivity or illness beliefs. There have been
attempts to tailor psychological interventions, mainly by providing basic
treatment modules and some optional modules. Which modules to follow was,
however, determined unsystematically (e.g. by patients* choice, regardless of
presence of maintaining factors) or by presence of factors potentially
maintaining the symptom. Presence of a potential maintaining factor does not
imply, however, that this factor and the main symptom are associated. Smart
technologies such as electronic diaries (ecological momentary assessments, EMA)
can establish temporal associations between (maintaining) factors and symptoms
of interest. EMA delivers personalized and contextualized information.
Therefore, EMA is primarily suited for personalizing interventions, adjusting
treatment on an individual level, as the specific maintaining factors in a
specific individual can be identified and targeted.

The aim of this proposal is to systematically personalize psychological
treatment, aimed at individual patient preferences and characteristics.
Tailoring therefore takes place on four levels:
1. Treatment indication: most studies select patients based on their symptom
level. A patient*s need for psychological care should also be considered,
however, and treatment indication should be determined by patients* experienced
burden from the symptom.
2. Treatment form: patients now receive either face-to-face, blended, or online
treatment according to availability. Research studies mostly include only one
treatment form. Tailoring comprises patients being able to choose for either
one of these three forms.
3. Focus and content of treatment: in current evidence-based treatments, every
patient receives the same treatment, aimed at decreasing symptom levels. Pilot
studies we undertook showed that ecological momentary assessments are capable
of registering individual symptom patterns over time and identifying factors
that maintain these symptoms in the individual patient. Thus, treatment will be
aimed at the specific factors that maintain symptoms in this specific
individual.
4. Treatment duration: the use of ecological momentary assessments during
treatment will enable the evaluation of treatment response and accordingly the
individual adjustment of treatment duration.
We expect this package of measures will make treatment more personalized and
thereby more effective, less burdensome and more efficient, with lower dropout
rates.

The primary objective of the proposed study is to test the efficacy of
personalized psychological care for improving functioning in cancer survivors
with severe and persistent depressive and/or fear of cancer recurrence and/or
cancer-related fatigue, and compare it to standard, non-personalized
psychological treatment. Hypothesized is that personalized psychological
treatment is more efficacious in improving functioning compared with standard,
non-personalized psychological treatment.

Secondary objective(s):
a. To determine the efficacy of personalized psychological treatment for
symptom level (fear of cancer recurrence, depression, fatigue), quality of
life, and goal attainment. Hypothesized is that personalized psychological
treatment will be more efficacious in reducing symptom levels, and improving
quality of life, compared with standard, non-personalized psychological
treatment. Goal attainment is an individualized outcome measure that is
suitable for problems that warrant an individual approach. Expected is that
personalized psychological treatment will be more efficacious in improving goal
attainment compared with standard, non-personalized psychological treatment;
b. To determine whether the expected positive effects of personalized
psychological treatment on patients* functioning are sustained at 12 months
after start of treatment;
c. To determine efficiency of treatment by evaluating treatment duration and
therapist time in personalized psychological treatment compared with standard,
non-personalized psychological treatment;
d. To evaluate dropout rates in the group receiving personalized psychological
treatment, compared with the group receiving standard, non-personalized
psychological treatment.

The study is designed as a multicenter randomized controlled trial with two
treatment arms: (a) personalized psychological treatment, versus (b) standard,
non-personalized psychological treatment. Participating therapists, each as a
separate unit, and participating patients will be randomly assigned to either
personalized psychological treatment or standard, non-personalized
psychological treatment. Patient functioning (primary outcome) and secondary
outcomes are evaluated at baseline (T0), 6 months (T1) and 12 months (T2) after
start of psychological treatment.

Personalized treatment group:

Psychological treatment will be systematically tailored on four levels:
1. Treatment indication: most studies select patients based on their symptom
level. A patient*s need for psychological care should also be considered,
however, and treatment indication should be determined by patients* experienced
burden from the symptom.
2. Treatment form: patients now receive either face-to-face, blended, or online
treatment according to availability. Research studies mostly include only one
treatment form. Tailoring comprises patients being able to choose for either
one of these three forms.
3. Focus and content of treatment: in current evidence-based treatments, every
patient receives the same treatment, aimed at decreasing symptom levels. Pilot
studies we undertook showed that ecological momentary assessments are capable
of registering individual symptom patterns over time and identifying factors
that maintain these symptoms in the individual patient. Thus, treatment will be
aimed at the specific factors that maintain symptoms in this specific
individual.
4. Treatment duration: the use of ecological momentary assessments during
treatment will enable the evaluation of treatment response and accordingly the
individual adjustment of treatment duration.

Personalized psychological treatment consists of the following steps:
1. Patient is referred for participation in this study via their treating
doctor or via self-referral
2. Screening and baseline questionnaires
3. Intake interview (verification of patients* need for psychological care;
identification of patients* most burdensome symptom). Following the standard
protocols of the treatment for fear of cancer recurrence, fatigue or
depression, additional questionnaires need to be filled out.
4. EMA assessment during 14 consecutive days. Auto-VAR analyses to identify
patients* individual maintaining factors on which to intervene.
5. Results of assessments will be discussed and verification of patients*
preference for face to face, blended, or internet therapy will take place.
6. Start treatment aimed at maintaining factors.
7. Evaluation of treatment response through EMA measurement, focused on
maintaining factors, measurement of symptoms, and individual treatment goals.
Based on the results (treatment had effect on maintaining factors; symptom
level is below predefined cutoff; patient reached his/her personal treatment
goals): discuss with patient whether treatment continuation or treatment end is
preferable.
8. In case of multiple symptoms: after ending treatment for the first symptom,
evaluation whether patient needs further treatment for the other symptoms
(questionnaire, need for care).
9. Duration of treatment will be variable (see (e)), but has a maximum of eight
months.

A concept personalized treatment protocol will be developed using evidence
based diagnosis-specific treatment protocols aimed at treating fear of cancer
recurrence, depression, and/or fatigue in patients with somatic conditions,
preferably patients with cancer. These are the standard protocols for treating
fear of cancer recurrence [21,31], the standard protocol for treating
depressive disorder with cognitive behavior therapy [31] and a treatment
protocol for treating fatigue in patients following cancer treatment [4,19].
These treatment protocols have been proven effective in nomothetic
(group-based) research. For personalizing the protocols, the following steps
will be taken:
1. The protocols will be divided into modules, based on the maintaining factors
these modules aim at. The result will be two general modules, essential for
every patient, and several optional modules, which will be only provided to
patients with these maintaining symptoms.
2. Each of the modules and corresponding maintaining factors will be linked to
one or more questions in the electronic diary. This will be piloted in regular
care, in 10 patients referred to the department of Medical Psychology of the
Academic Medical Center, who are regularly asked to fill out questionnaires as
part of their diagnostic phase.

Standard treatment group:
1. Patient is referred for participation in this trial via their treating
doctor or via self-referral
2. Screening and baseline questionnaires
3. Intake interview. Following the standard protocols of the treatment for fear
of cancer recurrence, fatigue or depression, additional questionnaires need to
be filled out
4. Results of assessments will be discussed
5. Start blended therapy for the symptom for which the score on the
accompanying questionnaire is above the cutoff
6. Patient receives the whole treatment protocol
7. At the end of treatment, questionnaire to assess symptom level.

Treatment protocols used for the standard, non-personalized treatment arm are
the same as those used for developing the personalized treatment protocol: (a)
ConquerFear protocol for treating fear of cancer recurrence [21]; (b) protocol
for treating depressive disorder [31]; and (c) treatment protocol for treating
fatigue in patients with cancer [4,19]. These treatment protocols have been
proven effective in nomothetic (group-based) research.

The risk of adverse events in the MATCH trial is negligible. The therapy will
be delivered by trained clinical psychologists who are highly skilled in
helping patients to manage distress and who have considerable expertise in
working with patients with cancer. Hence, only time investment is asked
regarding the completion of the questionnaires and psychological treatment, and
for the intervention group the completion of short diary measurements during 14
consecutive days. It is anticipated that patients in both treatment arms will
receive direct therapeutic benefits in the domains of anxiety, depressive or
fatigue symptoms.