BRAFm+ Metastatic melanoma
What makes it different, makes it vulnerable

When to test for BRAF mutation

Guidelines and algorithms for BRAF testing

Clinical decision-making in advanced and metastatic melanoma is evolving, as a result of new scientific and clinical trial evidence, and expert scientific discussion. Several guidelines and algorithms for BRAF testing have recently been published, to reflect these evaluations:

  • NCCN Guidelines Version 2.2016 Melanoma.1
  • Dummer et al. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.2
  • Pflugfelder A, et al. German Cancer Society guidelines: Malignant Melanoma S3-Guideline “Diagnosis, Therapy and Follow-up of Melanoma”. J Dtsch Dermatol Ges. 2013;Suppl 6:1–116.3
  • Gonzalez, D et al. BRAF mutation testing algorithm for vemurafenib treatment in melanoma: recommendations from an expert panel. Br J Dermatol. 2013;168:700–7.4

There are three points in the patient pathway when testing can be initiated2,5,6:

When BRAF testing can be triggered Which patients? Who requests the test?
1. Initial diagnosis of melanoma All melanoma patients Pathologist (reflex testing)
2. After initial MDT meeting High-risk patients Member of the MDT or pathologist in a ‘reflex manner’ following the initial classification of high-risk disease stage
3. Metastatic stage 4 melanoma Patients with advanced disease Clinician (newly acquired sample from metastasis or on primary tumour sample retrieved from archive)

MDT, multidisciplinary team

Reflex testing (option 1 and 2), when the pathologist is directly responsible for requesting the molecular analysis, permits rapid turnaround times, and prevents the need for retrieval of tissue samples at a later date, reducing staff time and therefore cost.5

It is important to note that these guidelines suggest BRAF mutation testing should be carried out in high risk patients or those with metastatic disease.1–4

This needs to be balanced against unnecessary testing in patients who will, in all likelihood, not need further treatment, or who may need treatment at a later date, when testing for mutations in alternative genes could be required.5

 

  1. NCCN Guidelines Version 2.2016 Melanoma. Available at: http://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf. Last accessed March 2016.
  2. Dummer R, et al. ESMO Guidelines Committee. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v126–32.
  3. Pflugfelder A, et al. German Cancer Society guidelines: Malignant Melanoma S3-Guideline “Diagnosis, Therapy and Follow-up of Melanoma”. J Dtsch Dermatol Ges. 2013;Suppl 6:1–116.
  4. Gonzalez D, et al. BRAF mutation testing algorithm for vemurafenib treatment in melanoma: recommendations from an expert panel. Br J Dermatol. 2013;168:700–7.
  5. Cree IA, et al. Guidance for laboratories performing molecular pathology for cancer patients. J Clin Pathol. 2014;67(11):923–31.
  6. Dummer R, et al. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;Suppl 7:vii86–91.