Compromised quality of life in adult patients who have received a radiation dose towards the basal part of the brain. A case-control study in long-term survivors from cancer in the head and neck region

Löfdahl Elisabet, Berg Gertrud, Johansson Karl-Axel, Zachrisson Maria, Malmgren Helge, Mercke Claes, Olsson Erik, Wiren Lena, Johannsson, Johannsson Gudmundur

Description

Adult patients with hypothalamic-pituitary disorders have compromised quality of life (QoL). Whether this is due to their endocrine consequences (hypopituitarism), their underlying hypothalamic-pituitary disorder or both is still under debate. The aim of this trial was to measure quality of life (QoL) in long-term cancer survivors who have received a radiation dose to the basal part of the brain and the pituitary. Methods Consecutive patients (n=101) treated for oropharyngeal or epipharyngeal cancer with radiotherapy followed free of cancer for a period of 4 to10 years were identified. Fifteen patients (median age 56 years) with no concomitant illness and no hypopituitarism after careful endocrine evaluation were included in a case-control study with matched healthy controls. Doses to the hypothalamic-pituitary region were calculated. QoL was assessed using the Symptom check list (SCL)-90, Nottingham Health Profile (NHP), and Psychological Well Being (PGWB) questionnaires. Level of physical activity was assessed using the Baecke questionnaire. Results The median accumulated dose was 1.9 Gy (1.5–2.2 Gy) to the hypothalamus and 2.4 Gy (1.8–3.3 Gy) to the pituitary gland in patients with oropharyngeal cancer and 6.0–9.3 Gy and 33.5–46.1 Gy, respectively in patients with epipharyngeal cancer (n=2). The patients showed significantly more anxiety and depressiveness, and lower vitality, than their matched controls. Conclusion In a group of long time survivors of head and neck cancer who hade received a low radiation dose to the hypothalamic-pituitary region and who had no endocrine consequences of disease or its treatment QoL was compromised as compared with well matched healthy controls.

Sujets

• Growth hormone
• Quality of life
• CNS

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 6
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Löfdahl et al. Radiation Oncology 2012, 7:179
http://www.ro-journal.com/content/7/1/179
RESEARCH Open Access
Compromised quality of life in adult patients who
have received a radiation dose towards the basal
part of the brain. A case-control study in
long-term survivors from cancer in the head and
neck region
1 1 2 3 4Elisabet Löfdahl , Gertrud Berg , Karl-Axel Johansson , Maria Leonsson Zachrisson , Helge Malmgren ,
1 5 3 3*Claes Mercke , Erik Olsson , Lena Wiren and Gudmundur Johannsson
Abstract
Background: Adult patients with hypothalamic-pituitary disorders have compromised quality of life (QoL). Whether
this is due to their endocrine consequences (hypopituitarism), their underlying hypothalamic-pituitary disorder or
both is still under debate. The aim of this trial was to measure quality of life (QoL) in long-term cancer survivors
who have received a radiation dose to the basal part of the brain and the pituitary.
Methods: Consecutive patients (n=101) treated for oropharyngeal or epipharyngeal cancer with radiotherapy
followed free of cancer for a period of 4 to10 years were identified. Fifteen patients (median age 56 years) with no
concomitant illness and no hypopituitarism after careful endocrine evaluation were included in a case-control study
with matched healthy controls. Doses to the hypothalamic-pituitary region were calculated. QoL was assessed using
the Symptom check list (SCL)-90, Nottingham Health Profile (NHP), and Psychological Well Being (PGWB)
questionnaires. Level of physical activity was assessed using the Baecke questionnaire.
Results: The median accumulated dose was 1.9 Gy (1.5–2.2 Gy) to the hypothalamus and 2.4 Gy (1.8–3.3 Gy) to the
pituitary gland in patients with oropharyngeal cancer and 6.0–9.3 Gy and 33.5–46.1 Gy, respectively in patients with
epipharyngeal cancer (n=2). The patients showed significantly more anxiety and depressiveness, and lower vitality,
than their matched controls.
Conclusion: In a group of long time survivors of head and neck cancer who hade received a low radiation dose to
the hypothalamic-pituitary region and who had no endocrine consequences of disease or its treatment QoL was
compromised as compared with well matched healthy controls.
Keywords: Growth hormone, Head-and-neck cancer, Quality of life, CNS, Low-dose-radiation, Long-term survivors
Background in adults has been associated with compromised
qualHypopituitarism in adults is mostly due to hypothalamic- ity of life (QoL) [1]. The reduced well-being
experipituitary tumours and its treatment with surgery, enced by many patients with hypopituitarism and
radiotherapy or both. Although carefully replaced with untreated GH deficiency has been one of the most
glucocorticoids, thyroxine and sex steroids, hypopituit- compelling arguments supporting GH replacement in
arism and untreated growth hormone (GH) deficiency adults [2]. This has, however, been questioned by some
studies suggesting that the pituitary disease itself or
* Correspondence: [e-mail]
3 the choice of therapy may explain the reduced QoL inDepartment of Endocrinology, Institute of Medicine, Sahlgrenska Academy,
University of Gothenburg, Sahlgrenska University Hospital, Grona straket 8, adult patients with hypopituitarism and untreated GH
SE-413 45, Sweden deficiency [3].
Full list of author information is available at the end of the article
© 2012 Löfdahl et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.Löfdahl et al. Radiation Oncology 2012, 7:179 Page 2 of 10
http://www.ro-journal.com/content/7/1/179
Radiation and radiotherapy is an important cause of were identified. Adults between 20 and 85 years of age
hypopituitarism and GH deficiency in adults [4]. When who had received radiotherapy for their cancer 4–10
brain areas are included in the radiation field, late reac- years earlier were eligible for the study. All patients had
tions with vascular and neuronal damage will occur. It is received radiotherapy to the neck and the base of the
well established that doses of more than 18–20 Gy to the skull; the histopathology for all tumours was squamous
hypothalamic-pituitary area will cause neuroendocrine cell carcinoma. Patients were excluded for further
anaconsequences and reduced QoL and cognitive function. lysis if they had significant nutritional difficulties or any
This is particularly well established in adult patients with other major consequences after previous treatment of
pituitary adenomas who have received radiotherapy in the primary disorder, had significant pulmonary disease
doses approximating 40 Gy [1]. These patients suffer or active malignancy, or were dependent regarding
activfrom low energy levels, lack of vitality, mental fatigue, ities of daily living. Patients with a known
neuroendopoor memory and concentration, and increased anxiety crine disorder, such as a gross hypothalamic-pituitary
and emotional reactions [1]. In such patients it is not lesion or previously verified anterior pituitary hormone
possible to differentiate to what extent the effects on deficiency, were also excluded from further analysis
QoL and cognitive function are endocrine consequences (Figure 1).
of radiotherapy, and to what extent they are due to Using the above selection criteria, 58 survivors were
radiation-induced brain damage in the hypothalamus. identified and invited to attend a pre-study visit to
The endocrine consequences of radiotherapeutic finalize their inclusion in the study. Clinical endocrine
effects on the hypothalamus are dose related [5]. Al- and evaluation was performed. Forty-eight patients came
though low dose exposure (<100mGy per fraction) has to this first visit. Fifteen patients without endocrine or
recently been suggested to cause cognitive impairment concomitant disorders or relapse of cancer then
conin children [6], information is unavailable on such low sented to be included in the case-controlled study.
Medose exposure in adults. Estimations concerning an in- dian time from radiation treatment to performance of
crease in secondary malignancies after low dose have the study was 6 years (range 4–10 years). See Table 1
been made [7], but other biological late effects, such as for a further summary of patients’ characteristics.
endocrine effects or factors known to affect QoL, have Fifteen healthy controls matched for age, sex, BMI,
not been well studied. and social status were recruited. Relatives or close
The prognosis for patients with cancers of the head friends were selected as controls in order to adjust for
and neck has improved during recent years allowing for socioeconomic status. Oral and written informed
cona more long-term follow-up of these patients. The sent was obtained from patients and controls before
causes of this include the introduction of hyper fractio- entering the study. The study was approved by the Ethics
nated accelerated radiotherapy (EBRT) and brachyther- Committee of the University of Gothenburg (No. S644-01).
apy (BT) in combination with chemotherapy [8]. BT is
often replaced by intensity modulated radiotherapy Cancer treatment
(IMRT). Irrespective of the radiotherapy technique used All patients had received external-beam radiotherapy
in patients with cancers of the head and neck, a small (EBRT) with a beam quality of 4–6 MV from linear
proportion of the dose will reach the basal part of the accelerators (Varian) using CT-assisted 3-D dose
planbrain. Earlier studies have shown disease specific long- ning (Cadplan System). The primary target volume was
term consequences of the disease and its treatment defined as gross target volume (GTV) with a margin of
[9-12]. However, in these studies the neuroendocrine 1.5–2 cm. An elective target volume was also defined,
consequences of radiation to the basal part of the brain mainly in the neck region. This means that treatment
have not been considered as a confounder. was divided into two parts, one cranial and one lower
The present patient population was therefore used as a (neck), with a division at the level of the hyoid bone. In
model to explore our research hypothesis that a relatively the lower volume there was a central shielding of the
low dose of radiotherapy towards the adult basal brain larynx, which also meant shielding of the central part of
will have a long-term impact on QoL independently of the thyroid gland. In treatment of the oropharynx the
the possible neuroendocrine consequences of such ther- cranial border is at the level of the palate, and when
apy. The data from this study of long-term survivors of treating the epipharynx the border is at the top of the
head and neck cancer may support this hypothesis. sella turcica. The dose from EBRT was either 40.8 Gy or
64.6 Gy (specified at the isocenter) to the primary target
Methods volume according to tumour stage by use of hyper
fracPatients tionated, accelerated fractionation. The schedule used
From the local database of the Department of Oncology was 1.7 Gy twice a day. There was a pause for 8–10 days
in 2002, 101 individuals with head and neck cancers after either 34.0 or 40.8 Gy. The dose to the electiveLöfdahl et al. Ra