3.1 Specialist diagnostic work-up

3.1 Specialist diagnostic work-up

The treatment team, after taking a thorough medical history and making a thorough medical examination of the patient, should undertake the following investigations under the guidance of a specialist.

All patients should undergo the following:

  • T1 weighted, T2 weighted, FLAIR, T2 weighted and post-contrast T1 weighted MRI should be performed. Diffusion-weighted imaging (DWI) should also be done. Advanced MR imaging techniques including MR spectroscopy and perfusion sequences are also helpful in imaging centres with expertise. Patients should undergo pre- and post-contrast MRIs and preferably advanced imaging with MR spectroscopy and MR perfusion sequences. Some centres may use PET scans to assist.
  • Order a tissue biopsy to reliably diagnose brain tumours:
    • The histological diagnosis of brain tumours should be undertaken by a neuropathologist or by an appropriately trained anatomical pathologist with experience in tumour neuropathology.
    • Tumours should be classified according to the latest World Health Organization classification of tumours of the central nervous system.

Molecular markers must be identified for an accurate diagnosis. Molecular testing may include identifying mutations in IDH, TERT, ATRX, H3K27M or codeletion of chromosome 1p and 19q depending on the tumour. This is an evolving field that is likely to change over the coming years.

Molecular testing is strongly advised for treatment planning (see section 3.2 for available tests).

Diagnostic investigations should be completed within one week of referral to a specialist. Note that molecular testing may take one to two weeks.

Five to 10 per cent of all cancers are due to a genetic predisposition. The features that suggest a genetic predisposition may include:

  • early age at onset
  • multiple primary cancers
  • a family history of similar or related cancers, neurofibromatosis type 1 or tuberous sclerosis.

If present, these features may indicate that familial genetic testing is appropriate.

In some cases certain pathological subtypes of cancer or tumour tests (immunohistochemistry or tumour genetic tests) may suggest an underlying inherited cancer predisposition.

Anyone diagnosed with cancer should have a detailed personal and family cancer history taken. Consult relevant guidelines to determine if referral to a familial cancer service is appropriate.

A familial cancer service assessment can determine if genetic testing is appropriate. Genetic testing is likely to be offered when there is at least a 10 per cent chance of finding a causative ‘gene error’ (pathogenic gene variant; previously called a mutation). Usually testing begins with a variant search in a person who has had cancer (a diagnostic genetic test). If a pathogenic gene variant is identified, variant-specific testing is available to relatives to see if they have or have not inherited the familial gene variant (predictive genetic testing).

Medicare funds some genetic tests via a Medicare Benefits Schedule (MBS) item number but most are not. Depending on the personal and family history, the relevant state health system may fund public sector genetic testing.

Pre-test counselling and informed consent is required before any genetic testing. In some states the treating team can offer ‘mainstream’ diagnostic genetic testing, after which referral is made to a familial cancer service if a pathogenic gene variant is identified. The familial cancer service can provide risk management advice, facilitate family risk notification and arrange predictive genetic testing for the family.

Visit the Centre for Genetics Education website for basic information about cancer in a family.

Pharmacogenetics describes how individual genetic differences can lead to differences in the way certain medicines interact with the body. These interactions can affect the effectiveness of medications and any side effects. Applying pharmacogenetics to treatment planning may help patients to be prescribed the most appropriate treatment at the optimal dose from the beginning of treatment (NHMRC 2013).