Cognitive functioning and health-related quality of life in long-term anaplastic oligondendroglioma and oligoastrocytoma survivors from the EORTC 26951 study: second follow-up

The addition of Procarbazine, Lomustine, and Vincristine (PCV) chemotherapy to
radiotherapy (RT) proved to be an effective treatment in terms of
progression-free and overall survival for newly diagnosed anaplastic
oligondendroglioma patients, particularly those with 1p/19q co-deletion. As
survival time increases, patients may experience late effects (i.e. side
effects that become apparent months or years after treatment has ended) caused
by anti-tumor treatment such as radiotherapy. These late effects, including
cognitive dysfunction, may subsequently impair the health-related quality of
life (HRQoL) of patients. Hence, if treatments that result in effective tumor
control are associated with cognitive impairments and worse HRQoL on the
long-term, longer survival may be less meaningful for patients. To date, little
is known about long-term HRQoL and neurocognitive functioning (NCF) in patients
with anaplastic oligodendrogliomas.

The initial results about the effect of the combination of RT and PCV on HRQoL
showed that the addition of PCV resulted in a short-term deterioration of HRQoL
(i.e. more nausea and vomiting), with no impact on the longer term. For
cognition, only results are available on the longer term (median 12 years after
randomization). Habets et al. showed that 30% of the long-term anaplastic
oligodendroglioma or oligoastrocytoma survivors without progression (n=27) had
severe cognitive impairments, and 44% mild to moderate impairments. Out of the
five patients with progression, three had severe cognitive impairment, one had
mild to moderate impairment and one had no impairment. This suggests that
glioma patients who respond favourably to first-line treatment might actually
be at risk for long-term treatment-related cognitive decline. Continued
information on NCF and HRQoL in long-term survivors could inform us further
about the late effects of treatment with RT and/or PCV in these patients.

Of the 32 anaplastic oligondendroglioma or oligoastrocytoma patients who were
included in the follow-up study by Habets et al., a subgroup is still alive.
Therefore, we propose to assess NCF and HRQoL, as well as some other relevant
patient-centred outcome measures (mood, fatigue, cognitive complaints, health
care utilization) in the long-term survivors of the EORTC 26951 study as a
second follow-up. Because patient-reported outcome measures may be difficult to
complete for patients who are incapacitated or have a poor health status,
patient-proxy HRQoL assessment will be considered as an acceptable alternative,
as the level of agreement between patient*s and proxy*s in assessing the
patient*s HRQoL is generally high. Since cognitive deficits in (long-term)
surviving glioma patients who underwent radiotherapy have been associated with
radiological abnormalities, we will also explore cerebral abnormalities in the
long-term survivors of the EORTC 26951 study.

Primary objective:
To assess NCF, HRQoL, mood, fatigue, cognitive complaints and health care
utilization in long-term surviving patients with anaplastic oligondendroglioma
and oligoastrocytoma.

Secondary objective:
To assess cerebral abnormalities in long-term surviving patients with
anaplastic oligondendroglioma and oligoastrocytoma.

We will perform an observational cross-sectional measurement of NCF, HRQoL,
mood, fatigue, cognitive complaints, health care utilization and cerebral
abnormalities in long-term surviving patients with anaplastic oligodendroglioma
and oligoastrocytoma who participated in the EORTC 26951 study, and were also
included in the follow-up study by Habets et al.

There are no direct benefits for participants in this study. This study will
provide new information on the quality of long-term survival in this patient
group. Nevertheless, filling in the questionnaires and undergoing the cognitive
tests may be tiresome. The participant burden is believed to be minimal, only
related to possible fatigue.