Practice changing studies have been published in late 2017 and 2018 on IDH wild-type diffuse astrocytoma (the new entity of WHO 2016 classification), and on treatment of brain metastases from melanoma.
A large retrospective study and a review by the International Consortium on CNS Tumor Taxonomy (C-IMPACT-Now)1 have established that diffuse astrocytomas of WHO grade II or III, that lack the molecular factor IDH mutation (positive prognostic factors), are an heterogeneous group of tumors, and in case there is amplification of EGFR, they are actually “baby glioblastomas” (grade IV), thus to be treated vigorously with chemoradiation.
Brain metastases from melanoma were historically associated with a dismal survival (2-10 months) despite conventional radio-chemotherapy. The prognosis has dramatically changed with the advent of immunotherapy with now a 4-year survival around 14%. The best results are observed in patients with small and asymptomatic brain metastases, and the most effective treatment seems a combination of two immune-checkpoint inhibitors such as nivolumab and ipilimumab 2-3.
Keypoints:
- IDH wild-type diffuse astrocytomas are molecularly heterogeneous.
- IDH wild-type diffuse astrocytomas of grade II-III WHO with EGFR amplification are “baby” glioblastomas.
- Brain metastases from melanoma are optimally treated by immunotherapy.
References:
Brat DJ, Aldape K, Colman H, Holland EC, Louis DN, Jenkins RB, Kleinschmidt-DeMasters BK, Perry A, Reifenberger G, Stupp R, von Deimling A, Weller M. cIMPACT-NOW update 3: recommended diagnostic criteria for "Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV". Acta Neuropathol. 2018 Nov;136(5):805-810.
Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, Brown MP, Wilmott JS, Edwards J, Gonzalez M, Scolyer RA, Menzies AM, McArthur GA. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018 May;19(5):672-681.
Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, Khushalani NI, Lewis K, Lao CD, Postow MA, Atkins MB, Ernstoff MS, Reardon DA, Puzanov I, Kudchadkar RR, Thomas RP, Tarhini A, Pavlick AC, Jiang J, Avila A, Demelo S, Margolin K. Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. N Engl J Med. 2018 Aug 23;379(8):722-730.