Chronic stress and Responsiveness to Immunotherapy for Metastasized Melanoma

Immunotherapy with checkpoint inhibitors in metastasized melanoma patients is a
relatively new treatment option that is effective in approximately 40% of the
cases. Whether people respond to immunotherapy is apparent after three months
and, until date, mostly unpredictable although age, gender, lactate
dehydrogenase (LDH) and WHO-performance score are found to be associated with
overall survival. Identifying additional alterable factors differentiating
responders from non-responders after immunotherapy is important as it may
direct the development of additional interventions and the allocation of scarce
medical and financial resources.
Recently, scholars and researchers have suggested that chronic stress may
impact the effectiveness of immunotherapy. The cause for this might be that
chronic stress is known to impact the immune system by the release of
glucocorticoids which suppresses immune reactions. Consequently, chronic stress
may weaken the efficacy of immunotherapy which is aimed at boosting the immune
system. Indirect and preliminary evidence supporting the link between chronic
stress and the effectiveness of immunotherapy is found in studies investigating
the impact of glucocorticoids on the effectiveness of immunotherapy in mouse as
well as in patients.

The present pilot study will examine whether chronic stress is related to
response to immunotherapy with checkpoint inhibitors for metastasized melanoma.
Stress will be assesed by Hair cortisol, Salivary cortisol and some validated
questionnaires (Eysenck Personality Questionnaire - Revised Short Scale, stress
subscale of the Four-Dimensional Symptom Questionnaire (4DSQ), The Center for
Epidemiological Studies Depression Scale (CES-D) and the State-scale of the
State Trait Anxiety Index (STAI).

In this observational cohort study both objective (i.e., hair cortisol and
salivary cortisol) and subjective measures (self-report questionnaire) of
stress will be assessed in patients with metastasized melanoma. Measurement
will take place before start of immunotherapy (baseline, T0) and at three (T1)
and six (T2) month after of start immunotherapy. At T1 and T2 responsiveness to
the immunotherapy is determined using radiological evaluation as part of
standard care. Furthermore, standard baseline characteristics will be analyzed
(WHO-score, age, gender, LDH etc).

Assessment will take place before start of immunotherapy and at 3 and 6 months
after start of immunotherapy. Patients have to donate hair and salivary samples
(both non-invasive) for cortisol assessment and complete a short questionnaire
at three time points. Time investment per patient will be a maximum of 10
minutes per assessment (30 minutes in total). No risks or adverse events are
expected from this study.