Medical assessment of adverse health outcomes in Dutch childhood cancer survivors; a nationwide project; DCOG-LATER Q2008 study;
Long-term renal effects in Dutch survivors of childhood cancer

Advances in diagnosis and treatment of childhood cancer over the last decades
have dramatically increased long-term survival. As a result, the numbers of
childhood cancer survivors (CCS) are growing and it has become increasingly
clear that the former disease and its treatment can significantly impair
long-term health. The need for long-term follow-up is uniformly recognized.
Research focusing on identification and characterization of high-risk
populations is an essential foundation on which to build evidence-based
recommendations for long-term follow-up. Furthermore, research focusing on more
accurate screening tests and effective interventions is needed to reduce excess
morbidity and mortality in CCS.

The SKION LATER Q2008 - renal study phocuses on late renal toxicity in CCS in
relation to (potentially) nefrotoxic modalities with varying doses and
administered at different ages.

Aim of the study is to assess
1) the prevalence of glomerular dysfunction and tubular dysfunction in
childhood cancer survivors treated with possible nefrotoxic therapy.
2) the treatment related risk factors for glomerular and/or tubular dysfunction
in childhood cancer survivors treated with possible nefrotoxic
therapy
3) the diagnostic value of cystatin C in detecting glomerular dysfunction in
childhood cancer survivors?
4) the relationship between glomerular function and hypertension
5) the relationship between renal factors and bone density (together with the
SKION-LATER Q2008-bone projectgroup)
6) the relationship between renal dysfunction and growth (together with the
SKION-LATER Q2008-endocrinology projectgroup)
7) the relationship between renal dysfunction and cardiovasculair risk
(together with the SKION-LATER Q2008-cardiology)

This cross-sectional study consists of an anamnesis, a physical examination
(weight, height, bloodpressure), a venapuncture and the provision of a urine
sample. All examinations are performed as part of regular patient follow-up
care as defined by the guidelines for screening for late renal toxicity in CCS.
In order to perform some additional blood and urine analyses for study purposes
some extra blood and urine will be collected for the patient. However, no extra
venapuncture will have to be performed. All study parts will be performed on
the same day during a visit to the Late Effects Outpatient Clinic for patient
follow-up care. For a sugroup of 100 survivors of the VUmc and AMC-cohort an
ambulant 24 hours bloodpressure measurement will take place.Collected data will
be stored anonymously in a national database and will eventually be related to
previous treatment data.

Patients will be invited to visit the Late Effects Outpatient Clinic for their
regular follow-up care according to the nationwide screening guidelines. During
this visit to the outpatient clinic they will undergo a physical examination
(weight, height, bloodpressure), a venapuncture and they will be asked to
provide a urine sample as part of their follow-up care. For study reasons some
additional blood will be drawn (8ml in 1000 patients and 2 ml in 2000 patients)
during the same venapuncture as that required for patient care. Therefore there
is no additional study risk and burden for the patient.

It is possible that the study will lead to new insights regarding the patients
health. If renal damage is established it is of benefit to the patient to know
about this so appropriate treatment can be initiated in order to improve
prognosis and reduce the number of complications in the long run.
In addition, the study will provide an increased insight into the risks and
extent of renal damage and its complications following childhood cancer in
general and after several treatment modalities in particular. This information
may be of great value to future patients having to undergo treatment for
childhood cancer which includes a (possible) nefrotoxic modality. For instance,
treatment protocols may, where possible, be adjusted in order to decrease
toxicity without reducing survival, better screeningmethods may become
available, and interventions may be applied sooner.

In order to fully evaluate the prevalence, extent, and progression of renal
damage following treatment of childhood cancer it is important to also look at
the relatively short term (5-10 jaar after diagnosis) damage and complications.
Prevalence and extent of damage found 5-10 years after diagnosis can then be
compared to the prevalence and extent of damage in a group of survivors who are
more than 10 years after diagnosis. The group of patients 5-10 years after
diagnosis in this study also includes minors, although this group is relatively
small (135 out of 3000). These minors will also be seen at the late effects
outpatients clinic for regular follow-up care which also includes a physical
examination, venapuncture and urine collection. Therefore, there is no
additional study risk or burden for minors either since blood for the study
will be collected during the same venapuncture required for follow-up care.