ABSTRACT
A 50-year-old male with advanced non-small-cell lung cancer was unable to have standard-of-care molecular testing performed at diagnosis as a result of inadequacy of the available tissue. A subsequently performed commercial liquid tumor biopsy (Foundation ACT®) revealed an epidermal growth factor receptor exon 19 deletion, but due to the progression of the tumor and rapid deterioration in the patient's performance status, a meaningful attempt at therapy directed to this recognized therapeutic target was not possible. This case provides important support for the relevance of liquid tumor biopsies in documenting highly clinically relevant molecular targets, particularly in the setting where limited solid tumor tissue is available for analysis.
ABSTRACT
UNLABELLED: Neuroendocrine tumors comprise a heterogeneous group of malignancies with a broad spectrum of clinical behavior. Poorly differentiated tumors follow an aggressive course with limited treatment options, and new approaches are needed. Oncogenic BRAF V600E (BRAF(V600E)) substitutions are observed primarily in melanoma, colon cancer, and non-small cell lung cancer, but have been identified in multiple tumor types. Here, we describe the first reported recurrent BRAF(V600E) mutations in advanced high-grade colorectal neuroendocrine tumors and identify a BRAF alteration frequency of 9% in 108 cases. Among these BRAF alterations, 80% were BRAF(V600E) Dramatic response to BRAF-MEK combination therapy occurred in two cases of metastatic high-grade rectal neuroendocrine carcinoma refractory to standard therapy. Urinary BRAF(V600E) circulating tumor DNA monitoring paralleled disease response. Our series represents the largest study of genomic profiling in colorectal neuroendocrine tumors and provides strong evidence that BRAF(V600E) is an oncogenic driver responsive to BRAF-MEK combination therapy in this molecular subset. SIGNIFICANCE: BRAF(V600E) is an established oncogenic driver, but significant disparities in response exist among tumor types. Two patients with treatment-refractory high-grade colorectal neuroendocrine tumors harboring BRAF(V600E) exhibited rapid and durable response to combined BRAF-MEK inhibition, providing the first clinical evidence of efficacy in this aggressive tumor type. Cancer Discov; 6(6); 594-600. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 561.
Subject(s)
Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Mutation , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/genetics , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins B-raf/genetics , Adult , Aged , Amino Acid Substitution , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy , Codon , Colorectal Neoplasms/drug therapy , Female , Humans , Molecular Targeted Therapy , Neoplasm Grading , Neoplasm Metastasis , Neuroendocrine Tumors/drug therapy , Positron Emission Tomography Computed Tomography , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Signal Transduction/drug effects , Treatment OutcomeABSTRACT
The occurrence of metastasis of a systemic neoplasm to an intracranial tumor is a rare phenomenon. Meningiomas have been reported as the most common intracranial tumor to harbor a systemic metastasis, with breast and lung carcinomas being the most common sites of origination. Here, we report a case of an adenocarcinoma metastasis of an adenosquamous lung carcinoma found within a meningioma, resulting in the patient's first clinical manifestations. We also review the literature for other cases of adenocarcinoma metastatic to a meningioma and suggest mechanisms that make meningiomas likely to harbor systemic metastases including increased vascularity, slow growth rate, increased hyaline content and expression of cell-cell adhesion molecules.
