medwireNews: The Guideline Development Group has created a set of UK guidelines to aid clinicians in the diagnosis and treatment of children and young people with adamantinomatous craniopharyngiomas.
The guidelines are based on evidence from 239 published primary studies and seven national or international evidence-based guidelines and were developed under the auspices of the UK Children’s Cancer and Leukaemia Group and the British Society for Paediatric Endocrinology and Diabetes.
Where there was insufficient evidence to make a recommendation, one was proposed, put through up to two Delphi consensus rounds and included if there was at least 70% agreement. The final guideline was reviewed by five independent reviewers and quality assured and endorsed by The Royal College of Paediatrics and Child Health Quality Improvement Committee.
Diagnosis
Studying people younger than 19 years of age, the guidelines recommend that assessment for suspected craniopharyngioma should routinely involve magnetic resonance imaging (MRI) with dedicated pituitary views in both sagittal and coronal planes. Additional computed tomography scans should be used when the diagnosis or extent of calcification is in doubt and to determine the extent of resection and overall surgical treatment strategy.
Preoperative grading, from MRI scanning, of hypothalamic involvement to inform hypothalamic-sparing surgery is important, say Hoong-Wei Gan (Great Ormond Street Hospital, London, UK) and the Guideline Development Group in The Lancet Diabetes & Endocrinology. “Use of the most replicated grading system decreases the risk of adipsia, hyperphagia, and obesity”, they add.
Given that most (80–90%) children with craniopharyngiomas will have hypothalamic–pituitary deficits when diagnosed, the guidelines recommend comprehensive endocrinology testing to determine adrenal status and identify diagnoses such as prolactinoma, secreting germ cell tumour, diabetes insipidus and hypothalamic syndrome.
Testing should include α-fetoprotein, β-human chorionic gonadotropin and prolactin, as well as insulin-like growth factor 1, thyroid-stimulating hormone, free thyroxine, luteinising hormone, follicle-stimulating hormone, testosterone and oestradiol, paired early morning plasma and urine osmolalities and electrolytes, and morning levels of cortisol and adrenocorticotropic hormone (ACTH) if no dexamethasone has been given.
Other investigations should include visual acuity testing and neurocognitive assessment, and the recommendations advise that “[w]here possible, a histological diagnosis should be obtained before definitive treatment unless appearances are clearly typical intraoperatively or in neurosurgical emergencies.”
Treatment
In terms of treatment, complete or subtotal resection is recommended over conservative management. However, complete resection should not be considered “where there is clear evidence of hypothalamic involvement on grading”, says the group.
The guidelines note that subtotal resection can be salvaged with adjuvant radiotherapy “without the increased risk of long-term morbidity and central diabetes insipidus, particularly in tumours with hypothalamic involvement.”
The group recommends perioperative dexamethasone for neuroprotection and for those not given it, routine use of preoperative stress doses of hydrocortisone until hypothalamic–pituitary–adrenal axis evaluation post-surgery.
Diagnoses to be aware of include central diabetes insipidus, iatrogenic intravenous hyperhydration, glycosuria, central adrenal insufficiency, inappropriate antidiuretic hormone secretion, iatrogenic water overload and cerebral salt-wasting syndrome in the presence of postoperative polyuria or hyponatraemia.
Upfront external beam radiotherapy should be considered for patients undergoing incomplete tumour resection, says the group, adding that it confers “no additional benefit” for those undergoing complete resection and should be delayed until tumour progression is evident.
High-energy proton beam therapy as a radiation treatment modality can be used, although the evidence quality for it is low, Gan et al note, while gamma knife radiosurgery should be avoided.
Other therapies to be avoided as primary treatment given insufficient or low-quality evidence are intracystic chemotherapies and interferon α-2b.
Post-treatment follow-up and management
Following surgery, MRI surveillance imaging is recommended within 3–6 months, and then at regular intervals. Visual acuity testing should also be offered within 3 months with ongoing follow-up.
The group highlights that “[t]here is an overwhelming consensus that lifelong endocrine follow-up is required, including transition to specialist adult neuroendocrine services.”
They recommend that basal and combined dynamic anterior pituitary function tests are offered within 6 weeks of treatment to assess growth hormone integrity, levels of ACTH and thyroid-stimulating hormone, as well as gonadotrophin axes if age appropriate. Dynamic function testing should be considered on several occasions during recovery.
Children with confirmed growth hormone deficiency can be offered recombinant human growth hormone in replacement doses, with evidence suggesting it does not increase the risk of tumour progression.
According to the guidelines, access to a multidisciplinary team is important to ensure specialist psychological, endocrine, exercise and dietary advice for the management of hypothalamic obesity, as well as the provision of sleep and behavioural neuropsychopharmacology services.
Gan and team discuss the management of recurrence, which they say “remains a considerable challenge and no high-quality evidence supports any treatment strategy.” They suggest further surgery and cyst drainage with the addition of radiotherapy.
Next steps
Concluding, Gan and team stress “the need for children and young people with craniopharyngiomas to be managed in a multidisciplinary setting, with access to national expertise, in conjunction with patients and their families to be able to weigh the risks and benefits of the various treatment options available.”
They point out that there are still gaps in evidence to underpin current management strategies, including “the long-term outcomes of proton beam therapy, the optimum timing of radiotherapy, the efficacy of intracystic therapies, the management of tumour progression, and the treatment of hypothalamic dysfunction.”
By Lucy Piper
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