COMPRehensive assessment of prevalence, risk factors and mechanisms of impaired medical and psychosocial health outcomes among Adolescents and Young Adults with cancer: the prospective observational COMPRAYA cohort study

Childhood cancer survivorship attracts attention globally, because successes in
treatment have led to increasing number of survivors who reach adulthood, in
which survivorship issues affecting health-related quality of life (HRQoL)
become prominent. Most pediatric patients are treated intensively with
irradiation and/or chemotherapy which put them at risk for early and/or late
adverse medical and psychosocial events. In contrast, much less is known from
adolescent and young adult (AYA) cancer patients, diagnosed between 18-39
years, who, with an 80% chance to survive, also have a long life ahead. AYA
cancer patients, much more than children, suffer from delay in diagnosis, lack
of centralization of care, age-adjusted expertise (*I am treated like my
74-year-old aunt*) and AYA follow-up care. AYAs typically present with a rare
tumor: either with a paediatric malignancy (e.g. acute lymphoblastic leukaemia,
paediatric brain tumors), a tumor of AYA age (e.g. Hodgkin*s disease, germ cell
cancer, melanoma, thyroid cancer) or, unexpectedly, with an adult tumor (e.g.
gastrointestinal, lung, breast carcinomas). Next to these differences in
epidemiology, tumor biology, developmental challenges (e.g. forming
relationships, becoming financially independent, having children) and treatment
regimens differ between AYAs and children, and therefore findings derived from
childhood cancer survivors cannot be extrapolated to AYAs. Furthermore, novel
treatments with targeted agents or immunotherapy are more likely to be
administrated to AYAs compared to children. Finally, a rare group of incurable
AYA cancer patients will survive for many years, for whom health outcome and
supportive care intervention data are lacking.

(Inter)nationally, cohort studies exist that address many relevant issues, but
all from the perspective of tumor histology, rather than an AYA age-specific
perspective. These tumor-specific cohorts do not specifically address unique
issues such as:
(1) Age-specific health outcomes like fertility, late toxicity, family
functioning, employment;
(2) Genetic risk factors and AYA tumor genetics;
(3) Tumor types with an incurable, protracted behaviour at this young age;
(4) Age-adjusted early interventions

Globally, so far, the identification of AYA patient subgroups that might be
more susceptible to poor health outcomes has not been systematically addressed.
The role of sociodemographic and treatment-associated risks, external exposures
(e.g. lifestyle) and host factors (e.g. genetic, biological, physiological); or
combinations of influences for impaired (age-specific) health outcomes, remains
largely unknown. Understanding who is at risk and why will support the
development of evidence-based AYA prevention, treatment and supportive care
programs and guidelines, in co-creation with AYA cancer patients.

To examine the prevalence, risk factors and mechanisms of impaired health
outcomes (short- and long-term medical and psychosocial effects and late
effects) over time among a population-based sample of AYA cancer patients.

Primary Objective:
- To identify individual, environmental, biological and psychological
characteristics of AYA cancer patients who are at high risk for impaired
medical and psychosocial health outcomes. In other words: To develop a
prediction model for impaired medical and psychosocial health outcomes (at
baseline, 2-, 5- and 10-year follow-up).

Secondary Objective(s):
-To assess the prevalence of impaired (age-specific) medical (e.g. second
tumour) and psychosocial (e.g. social isolation) health outcomes at each time
point (at baseline, 2-, 5- and 10-year follow-up).

Exploratory Objective(s):
-To analyse the course of medical and psychosocial health outcomes over time
(all timepoints needed)
-To analyse mediating mechanisms associated with impaired health outcomes in
AYA cancer patients (at baseline, 2-, 5- and 10-year follow-up).

Other Objective(s):
-To form a prospective observational cohort of patients diagnosed with cancer
at AYA age, and follow them over time until death.

This is a dynamic prospective study consisting of two study arms namely;
COMPRAYA 1.0 and COMRAYA 2.0.

Participating AYAs will be followed over several years to assess their health
outcomes. We do this by asking these patients at the individual level to
complete an annual questionnaire. In addition, in COMPRAYA 1.0, hair, blood and
stool samples will also be taken together with the measurement og the vital
parameters, at three time points, namely in the first 6 months after diagnosis,
2 and 5 years after diagnosis. Participants in COMPRAYA 2.0 will only be asked
to give blood once and to complete the questionnaires up to a maximum of 10
years after diagnosis.
Also, if the patient gives permission, medical data from the electronic patient
record, the Dutch cancer registry and other health-related registrations will
be collected.
Tumor tissue can also be used.

At participating hospitals, AYAs will be invited to participate in COMPRAYA.

COMPRAYA 1.0:
At the start of the study, the AYA will sign a consent form for:
(1) Collection of medical data from the electronic patient record, the Dutch
cancer registry and other health-related registries (consent linkage);
(2) Completion of validated questionnaires on (age-specific) health outcomes;

(3) Use of tumor tissue known to PALGA;
(4) Blood collection, storage and subsequent central analysis;
(5) Hair, stool collection, storage and subsequent analysis
(6) Hospital visit to measure vital parameters (body composition, strength);

COMPRAYA 2.0
Based on selection from the NKR, appropriate participants will receive an
invitation. They can give consent for participation either digitally or on
paper. Following this consent, the participant will be contacted for an
appointment to draw blood. The questionnaire can further be completed online or
on paper.

On an individual level, patients who participate are asked to complete
questionnaires on an annual basis for at least 10 years. All sample collections
will take place at three time points: 0-6 months after diagnosis (baseline), 2
and 5 years; except blood for DNA analyses which will only take place at
baseline. The collection of blood, hair and faeces at three occasions is
minimally invasive and the risks of blood draws, hair and fecal sampling are
negligible. All safety measures and procedures will be performed according to
local guidelines. Patients will not experience direct benefit from
participation in the COMPRAYA study.

By participating, patients will contribute to a better insight in the
prevalence of impaired medical and psychosocial (age-specific) health outcomes
in AYA and evidence on factors associated with these health outcomes. This will
lead to better and more personalized cancer care and supportive care tools for
future AYA cancer patients.