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J Natl Compr Canc Netw. 2019 Apr 1;17(4):297-301. doi: 10.6004/jnccn.2019.7291.

Squamous Cell Transformation of Primary Lung Adenocarcinoma in a Patient With EML4-ALK Fusion Variant 5 Refractory to ALK Inhibitors.

Author information

1
aDivision of Hematology/Oncology, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento.
2
bUniversity of California Davis Comprehensive Cancer Center, Sacramento.
3
cDepartment of Pathology and Laboratory Medicine and Genomic Shared Resource.
4
dDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, and.
5
eDepartment of Radiology, University of California Davis School of Medicine, Sacramento.
6
fDepartment of Radiation Oncology, University of California Davis Comprehensive Cancer Center, Sacramento.
7
gDepartment of Pathology, Kaiser Permanente Vallejo Medical Center, Vallejo; and.
8
hSutter Davis Medical Group, Davis, California.

Abstract

Histologic transformation from adenocarcinoma to squamous cell carcinoma in lung cancer has not been reported as a mechanism of resistance to ALK inhibition. This report describes the clinical course of a female former light smoker with metastatic lung adenocarcinoma whose tumor underwent histologic transformation from a well-differentiated lung adenocarcinoma to a well-differentiated lung squamous cell carcinoma in the same location at the left mainstem bronchus while maintaining the ALK fusion oncogene without any resistance mutations. After experiencing disease progression while on crizotinib, the patient participated in clinical trials that provided early access to the novel ALK inhibitors ceritinib and alectinib before they were commercially available. Tumor recurrence occurred at the primary and metastatic central nervous system sites (ie, brain and spine). At tumor progression, liquid biopsy and tumor genomic profiling of plasma cell-free DNA next-generation sequencing (NGS) provided an accurate diagnosis with a short turnaround time compared with the tissue-based targeted capture NGS. The patient received several courses of radiation primarily to the brain and spine during her disease course. Her disease did not respond to the immune checkpoint inhibitor nivolumab, and she died on home hospice approximately 4 years after diagnosis. This case supports the importance of both histopathologic assessment and comprehensive genomic profiling in selecting appropriate treatment for patients with refractory, metastatic, ALK oncogene-driven non-small cell lung cancer. Use of symptom-directed radiation in tandem with ALK inhibitors contributed to the disease and symptomatic control and prolonged survival in this patient.

PMID:
30959466
DOI:
10.6004/jnccn.2019.7291

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