Dramatic Response of BRAF V600E Mutant Papillary Craniopharyngioma to Targeted Therapy.
We recently reported that BRAF V600E is the principal oncogenic driver of papillary craniopharyngioma, a highly morbid intracranial tumor commonly refractory to treatment. Here, we describe our treatment of a man age 39 years with multiply recurrent BRAF V600E craniopharyngioma using dabrafenib (150mg, orally twice daily) and trametinib (2mg, orally twice daily). After 35 days of treatment, tumor volume was reduced by 85%. Mutations that commonly mediate resistance to MAPK pathway inhibition were not detected in a post-treatment sample by whole exome sequencing. A blood-based BRAF V600E assay detected circulating BRAF V600E in the patient's blood. Re-evaluation of the existing management paradigms for craniopharyngioma is warranted, as patient morbidity might be reduced by noninvasive mutation testing and neoadjuvant-targeted treatment.
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Priscilla K
PK
Brastianos
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Ganesh M
GM
Shankar
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Corey M
CM
Gill
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Amaro
A
Taylor-Weiner
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Naema
N
Nayyar
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
David J
DJ
Panka
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Ryan J
RJ
Sullivan
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Dennie T
DT
Frederick
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Malak
M
Abedalthagafi
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Pamela S
PS
Jones
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Ian F
IF
Dunn
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Brian V
BV
Nahed
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Javier M
JM
Romero
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
David N
DN
Louis
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Gad
G
Getz
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Daniel P
DP
Cahill
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Sandro
S
Santagata
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
William T
WT
Curry
Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).
Fred G
FG
Barker
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003397:Craniopharyngioma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D003399:Craniotomy; D065426:Cytoreduction Surgical Procedures; D004334:Drug Administration Schedule; D018698:Glutamic Acid; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics; D018365:Neoplasm, Residual / Q000601:surgery; D010091:Oximes / Q000008:administration & dosage; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics*; D011728:Pyridones / Q000008:administration & dosage; D011744:Pyrimidinones / Q000008:administration & dosage; D016896:Treatment Outcome; D014633:Valine
D007093:Imidazoles; D010091:Oximes; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; D018698:Glutamic Acid; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine; C561627:dabrafenib