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RET Fusion Lung Carcinoma: Response to Therapy and Clinical Features in a Case Series of 14 Patients

Authors :
Milton Saute
Keren Paz
Maya Ilouze
Mor Moskovitz
Rivka Katznelson
Doron Lipson
Lior Soussan Gutman
Nir Peled
Elizabeth Dudnik
Mira Wolner
Hadas Gantz Sorotsky
Hovav Nechushtan
Vincent A. Miller
Assaf Moore
Amanda Katz
V. Neiman
Addie Dvir
Julia A. Elvin
Maya Gottfried
Noa Gordon
Michal Sarfaty
Siraj M. Ali
Source :
Clinical lung cancer. 18(4)
Publication Year :
2016

Abstract

Background RET (rearranged during transfection) fusions have been reported in 1% to 2% of lung adenocarcinoma (LADC) cases. In contrast, KIF5B-RET and CCDC6-RET fusion genes have been identified in 70% to 90% and 10% to 25% of tumors, respectively. The natural history and management of RET-rearranged LADC are still being delineated. Materials and Methods We present a series of 14 patients with RET-rearranged LADC. The response to therapy was assessed by the clinical response and an avatar model in 2 cases. Patients underwent chemotherapy, targeted therapy, and immunotherapy. Results A total of 14 patients (8 women; 10 never smokers; 4 light smokers; mean age, 57 years) were included. KIF5B-RET and CCDC6-RET variants were diagnosed in 10 and 4 cases, respectively. Eight patients had an early disseminated manifestation, seven with KIF5B-RET rearranged tumor. The features of this subset included bilateral miliary lung metastases, bone metastases, and unusual early visceral abdominal involvement. One such patient demonstrated an early and durable complete response to cabozantinib for 7 months. Another 2 patients treated with cabozantinib experienced a partial response, with rapid significant clinical improvement. Four patients with tumors harboring CCDC6-RET and KIF5B-RET fusions showed pronounced and durable responses to platinum-based chemotherapy that lasted for 8 to 15 months. Two patients' tumors showed programmed cell death ligand 1-positive staining but did not respond to pembrolizumab. The median overall survival was 22.8 months. Conclusion RET-rearranged LADC in our series tended to occur as bilateral disease with early visceral involvement, especially with KIF5B fusion. Treatment with cabozantinib achieved responses, including 1 complete response. However, further studies are required in this group of patients.

Details

ISSN :
19380690
Volume :
18
Issue :
4
Database :
OpenAIRE
Journal :
Clinical lung cancer
Accession number :
edsair.doi.dedup.....47dc0e0e7303f9d6587e44c46cc6961c