Nasoethmoidal Intestinal-Type Adenocarcinoma Treated with Cetuximab: Role of Liquid Biopsy and BEAMing in Predicting Response to Anti-Epidermal Growth Factor Receptor Therapy

Abstract

Sinonasal intestinal‐type adenocarcinomas (SNS‐ITAC) are very rare tumors that resemble colorectal cancer in many of their pathological and molecular characteristics. Indeed, in most published series, 10%–14% of SNS‐ITAC harbor mutations in KRAS. There is no standard systemic treatment in recurrent or metastatic SNS‐ITAC, and there is no evidence of the use of any targeted agent in this entity. We present the case of a recurrent nasoethmoidal ITAC informed as RAS and BRAF wild‐type by standard real‐time polymerase chain reaction methods and treated with first‐line cetuximab and irinotecan without response. Circulating tumor cells coupled to highly sensitive DNA analyses unveiled a mutation in KRAS exon 2 codon 12. Subsequent studies in the primary tumor using BEAMing detected a mutation in the same codon, confirming the KRAS mutated status of the tumor, and possibly explaining the absence of treatment response. This case exemplifies how liquid biopsy can aid in the correct and real‐time molecular characterization of tumors even in a rare nonmetastatic cancer of the head and neck. Key Points Sinonasal intestinal type adenocarcinomas (SNS‐ITAC) are rare tumors that commonly develop after a prolonged exposure to organic dusts (wood, leather, etc.), and that resemble colorectal cancer in some of their morphological and molecular characteristics. KRAS mutations have been described in 10%–14% in most series. However, its predictive value for guiding treatment decisions with targeted therapies (i.e., anti‐epidermal growth factor receptor [EGFR] therapy) has not been defined. The first case of an SNS‐ITAC treated with anti‐EGFR therapy (cetuximab) is reported. Analysis of DNA from circulating tumor cells (CTCs) unveiled a mutation in KRAS not detected by standard methods in the primary tumor. However, RAS analysis using BEAMing detected a mutation in the primary tumor in the same codon of KRAS originally detected in CTCs, altogether possibly explaining the lack of treatment response. Liquid biopsy may allow for an accurate molecular diagnosis in rare, organ‐confined tumors where few therapeutic options exist. Highly sensitive molecular diagnostics may aid in better characterizing rare entities harboring potentially druggable targets.

Precision Medicine in the Treatment of Malignancies Involving the Ventral Skull Base: Present and Future

“…In view of its mutational profile, which is associated with a low rate of EGFR, HER2, KRAS, and BRAF mutations and a high rate of EGFR copy number gain, ITAC is theoretically a good candidate for anti-EGFR therapy [22][23][24]. However, real-life experience is scarce and less encouraging in this regard [25]. Since the gene MET is frequently mutated (64%), MET inhibitors potentially represent an attractive solution [26,27].…”

Liquid Biopsy in Head and Neck Cancer: Current Evidence and Future Perspective on Squamous Cell, Salivary Gland, Paranasal Sinus and Nasopharyngeal Cancers

“…Our group published the case of a patient with recurrent ITAC in whom liquid biopsy using the IsoFlux EPCAM-based microfluidic technology detected 26 CTC. Genomic analysis of CTC DNA using castPCR revealed a mutation in KRAS G12A that was retrospectively also detected in the primary tumor using BEAMing technology [ 63 ].…”

Detection and clinical significance of circulating tumor cells in colorectal cancer

“…CTCs exist before tumor lesions can be detected by medical imaging examination [ 19 ]. Patients with advanced tumors will typically have only 1 CTC out of 1 × 10 6 neutrophils in 1 mL of peripheral blood, and the number of CTCs in early-stage patients is even lower [ 20 ].…”