PMID- 38525319
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240326
IS  - 2666-3643 (Electronic)
IS  - 2666-3643 (Linking)
VI  - 5
IP  - 4
DP  - 2024 Apr
TI  - RET Fusion Testing in Patients With NSCLC: The RETING Study.
PG  - 100653
LID - 10.1016/j.jtocrr.2024.100653 [doi]
LID - 100653
AB  - INTRODUCTION: RET inhibitors with impressive overall response rates are now 
      available for patients with NSCLC, yet the identification of RET fusions remains 
      a difficult challenge. Most guidelines encourage the upfront use of 
      next-generation sequencing (NGS), or alternatively, fluorescence in situ 
      hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) 
      when NGS is not possible or available. Taken together, the suboptimal performance 
      of single-analyte assays to detect RET fusions, although consistent with the 
      notion of encouraging universal NGS, is currently widening some of the clinical 
      practice gaps in the implementation of predictive biomarkers in patients with 
      advanced NSCLC. METHODS: This situation prompted us to evaluate several RET 
      assays in a large multicenter cohort of RET fusion-positive NSCLC (n = 38) to 
      obtain real-world data. In addition to RNA-based NGS (the criterion standard 
      method), all positive specimens underwent break-apart RET FISH with two different 
      assays and were also tested by an RT-PCR assay. RESULTS: The most common RET 
      partners were KIF5B (78.9%), followed by CCDC6 (15.8%). The two RET NGS-positive 
      but FISH-negative samples contained a KIF5B(15)-RET(12) fusion. The three RET 
      fusions not identified with RT-PCR were AKAP13(35)-RET(12), KIF5B(24)-RET(9) and 
      KIF5B(24)-RET(11). All three false-negative RT-PCR cases were FISH-positive, 
      exhibited a typical break-apart pattern, and contained a very high number of 
      positive tumor cells with both FISH assays. Signet ring cells, psammoma bodies, 
      and pleomorphic features were frequently observed (in 34.2%, 39.5%, and 39.5% of 
      tumors, respectively). CONCLUSIONS: In-depth knowledge of the advantages and 
      disadvantages of the different RET testing methodologies could help clinical and 
      molecular tumor boards implement and maintain sensible algorithms for the rapid 
      and effective detection of RET fusions in patients with NSCLC. The likelihood of 
      RET false-negative results with both FISH and RT-PCR reinforces the need for 
      upfront NGS in patients with NSCLC.
CI  - (c) 2024 The Authors.
FAU - Conde, Esther
AU  - Conde E
AD  - Hospital Universitario 12 de Octubre, Madrid, Spain.
AD  - Universidad Complutense, Madrid, Spain.
AD  - Research Institute Hospital 12 de Octubre (i+12), Madrid, Spain.
AD  - Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain.
FAU - Hernandez, Susana
AU  - Hernandez S
AD  - Hospital Universitario 12 de Octubre, Madrid, Spain.
AD  - Research Institute Hospital 12 de Octubre (i+12), Madrid, Spain.
FAU - Rodriguez Carrillo, Jose Luis
AU  - Rodriguez Carrillo JL
AD  - Hospital Universitario Infanta Sofia, Madrid, Spain.
FAU - Martinez, Rebeca
AU  - Martinez R
AD  - Hospital Quiron Salud, Madrid, Spain.
FAU - Alonso, Marta
AU  - Alonso M
AD  - Hospital Universitario 12 de Octubre, Madrid, Spain.
AD  - Research Institute Hospital 12 de Octubre (i+12), Madrid, Spain.
FAU - Curto, Daniel
AU  - Curto D
AD  - Hospital Universitario 12 de Octubre, Madrid, Spain.
FAU - Jimenez, Beatriz
AU  - Jimenez B
AD  - Hospital Universitario Fuenlabrada, Madrid, Spain.
FAU - Caminoa, Alejandra
AU  - Caminoa A
AD  - Hospital Universitario Ramon y Cajal, Madrid, Spain.
FAU - Benito, Amparo
AU  - Benito A
AD  - Hospital Universitario Ramon y Cajal, Madrid, Spain.
FAU - Garrido, Pilar
AU  - Garrido P
AD  - Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain.
AD  - Hospital Universitario Ramon y Cajal, Madrid, Spain.
FAU - Clave, Sergi
AU  - Clave S
AD  - Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain.
AD  - Hospital del Mar, Barcelona, Spain.
FAU - Arriola, Edurne
AU  - Arriola E
AD  - Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain.
AD  - Hospital del Mar, Barcelona, Spain.
FAU - Esteban-Rodriguez, Isabel
AU  - Esteban-Rodriguez I
AD  - Hospital Universitario La Paz, Madrid, Spain.
FAU - De Castro, Javier
AU  - De Castro J
AD  - Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain.
AD  - Hospital Universitario La Paz, Madrid, Spain.
AD  - Instituto de Investigacion Sanitaria del Hospital Universitario La Paz (IdiPAZ), 
      Madrid, Spain.
FAU - Sansano, Irene
AU  - Sansano I
AD  - Hospital Universitario Vall d'Hebron, Barcelona, Spain.
FAU - Felip, Enriqueta
AU  - Felip E
AD  - Hospital Universitario Vall d'Hebron, Barcelona, Spain.
FAU - Rojo, Federico
AU  - Rojo F
AD  - Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain.
AD  - Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Madrid, 
      Spain.
FAU - Domine, Manuel
AU  - Domine M
AD  - Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Madrid, 
      Spain.
AD  - Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain.
FAU - Abdulkader, Ihab
AU  - Abdulkader I
AD  - Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
FAU - Garcia-Gonzalez, Jorge
AU  - Garcia-Gonzalez J
AD  - Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
FAU - Teixido, Cristina
AU  - Teixido C
AD  - Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer 
      (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
FAU - Reguart, Noemi
AU  - Reguart N
AD  - Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer 
      (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
FAU - Compan, Desamparados
AU  - Compan D
AD  - Hospital Clinico Universitario, Valencia, Spain.
FAU - Insa, Amelia
AU  - Insa A
AD  - Hospital Clinico Universitario, Valencia, Spain.
FAU - Mancheno, Nuria
AU  - Mancheno N
AD  - Hospital Universitario y Politecnico La Fe, Valencia, Spain.
FAU - Palanca, Sarai
AU  - Palanca S
AD  - Hospital Universitario y Politecnico La Fe, Valencia, Spain.
FAU - Juan-Vidal, Oscar
AU  - Juan-Vidal O
AD  - Hospital Universitario y Politecnico La Fe, Valencia, Spain.
FAU - Baixeras, Nuria
AU  - Baixeras N
AD  - Hospital Universitari de Bellvitge, L'Hospitalet, Barcelona, Spain.
FAU - Nadal, Ernest
AU  - Nadal E
AD  - Catalan Institute of Oncology, L'Hospitalet, Barcelona, Spain.
FAU - Cebollero, Maria
AU  - Cebollero M
AD  - Hospital General Universitario Gregorio Maranon, Madrid, Spain.
FAU - Calles, Antonio
AU  - Calles A
AD  - Hospital General Universitario Gregorio Maranon, Madrid, Spain.
FAU - Martin, Paloma
AU  - Martin P
AD  - Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain.
AD  - Instituto de Investigacion Sanitaria Hospital Universitario Puerta de Hierro, 
      Madrid, Spain.
FAU - Salas, Clara
AU  - Salas C
AD  - Hospital Universitario Puerta de Hierro, Madrid, Spain.
FAU - Provencio, Mariano
AU  - Provencio M
AD  - Hospital Universitario Puerta de Hierro, Madrid, Spain.
FAU - Aranda, Ignacio
AU  - Aranda I
AD  - Hospital General Universitario Dr. Balmis - Instituto de Investigacion Sanitaria 
      y Biomedica de Alicante (ISABIAL), Alicante, Spain.
FAU - Massuti, Bartomeu
AU  - Massuti B
AD  - Hospital General Universitario Dr. Balmis - Instituto de Investigacion Sanitaria 
      y Biomedica de Alicante (ISABIAL), Alicante, Spain.
FAU - Lopez-Vilaro, Laura
AU  - Lopez-Vilaro L
AD  - Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
FAU - Majem, Margarita
AU  - Majem M
AD  - Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
FAU - Paz-Ares, Luis
AU  - Paz-Ares L
AD  - Hospital Universitario 12 de Octubre, Madrid, Spain.
AD  - Universidad Complutense, Madrid, Spain.
AD  - Research Institute Hospital 12 de Octubre (i+12), Madrid, Spain.
AD  - Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain.
FAU - Lopez-Rios, Fernando
AU  - Lopez-Rios F
AD  - Hospital Universitario 12 de Octubre, Madrid, Spain.
AD  - Universidad Complutense, Madrid, Spain.
AD  - Research Institute Hospital 12 de Octubre (i+12), Madrid, Spain.
AD  - Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain.
LA  - eng
PT  - Journal Article
DEP - 20240220
PL  - United States
TA  - JTO Clin Res Rep
JT  - JTO clinical and research reports
JID - 101769967
PMC - PMC10957499
OTO - NOTNLM
OT  - FISH
OT  - Lung carcinoma
OT  - Next-generation sequencing
OT  - RET fusions
OT  - RT-PCR
COIS- Dr. Conde has received research funding from Eli Lilly, 
      10.13039/100004325AstraZeneca, and 10.13039/100011033ThermoFisher Scientific; and 
      honoraria from Pfizer, Roche, AstraZeneca, Janssen, and Eli Lilly. Dr. Hernandez 
      has received research funding from Eli Lilly, AstraZeneca, and ThermoFisher 
      Scientific, and honoraria from Pfizer, Roche, AstraZeneca, ThermoFisher 
      Scientific, and Eli Lilly. Mr. Alonso has received research funding from 
      AstraZeneca, and honoraria from Pfizer, Roche, and AstraZeneca. Dr. Jimenez has 
      received honoraria from Roche. Dr. Garrido has received research grants from 
      10.13039/100002429Amgen, AstraZeneca, Blueprint, 10.13039/100002491Bristol-Myers 
      Squibb, Boehringer Ingelheim, 10.13039/501100002973Daiichi-Sankyo, 
      10.13039/100004330GlaxoSmithKline, 10.13039/100005565Janssen, IO Biotech, Eli 
      Lilly, 10.13039/100009947Merck Sharp & Dohme, 10.13039/100004337Roche, Takeda; 
      and honoraria from AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, 
      Boehringer Ingelheim, Daiichi-Sankyo, GlaxoSmithKline, Janssen, Eli Lilly, Merck 
      Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, Takeda, Medscape, and Touch 
      Medical. Dr. Clave has received honoraria from AstraZeneca, Pfizer, Roche, Eli 
      Lilly, and Takeda. Dr. Arriola has received honoraria from AstraZeneca, 
      Boehringer Ingelheim, Pfizer, Roche/Genentech, Eli Lilly and Company, Novartis, 
      Takeda, Merck Sharp & Dohme, Bayer, and Bristol Myers Squibb. Dr. 
      Esteban-Rodriguez has received honoraria from AstraZeneca, Pfizer, and Merck 
      Sharp & Dohme. Dr. De Castro has received honoraria from AstraZeneca, Bristol 
      Myers Squibb, Hoffmann- La Roche, Merck Sharp and Dohme, Boehringer-Ingelheim, 
      Janssen, Eli Lilly, Sanofi, Takeda, Pfizer, Glaxo, and Gilead. Dr. Sansano has 
      received honoraria from F. Hoffmann La Roche AG, Merck Sharp & Dohme, Pfizer, 
      Takeda, AstraZeneca, and Boehringer Ingelheim. Dr. Felip has received honoraria 
      from AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol 
      Myers Squibb, Daiichi-Sankyo, Eli Lilly, F. Hoffmann - La Roche, Gilead, Glaxo 
      Smith Kline, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, Merck 
      Sharp & Dohme, Novartis, Peptomyc, Peervoice, Pfizer, Regeneron, Sanofi, Takeda, 
      Turning Point, and Touch Oncology. Dr. Rojo has received research funding from 
      10.13039/100004337Roche, AstraZeneca, Menarini, 10.13039/100004336Novartis, 
      10.13039/100004334Merck, Merck Sharp & Dohme, Bristol-Myers Squibb, 
      10.13039/100004319Pfizer, GlaxoSmithKline, Palex, Amgen, 
      10.13039/100004322Agilent, and Janssen, and honoraria from Roche, AstraZeneca, 
      Menarini, Novartis, Merck, Merck Sharp & Dohme, Bristol-Myers Squibb, Pfizer, 
      GlaxoSmithKline, Palex, Amgen, Agilent, Janssen. Dr. Domine has received 
      honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, 
      Takeda, Merck Sharp & Dohme, and Bristol Myers Squibb. Dr. Abdulkader has 
      received honoraria from AstraZeneca, Eli Lilly, Pfizer, Roche, Merck Sharp & 
      Dohme, Bristol Myers Squibb, Takeda, and Agilent Technologies S.A. Dr. 
      Garcia-Gonzalez has received honoraria from Amgen, AstraZeneca, Boehringer 
      Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Roche, Sanofi, 
      Pierre Fabre, Eli Lilly, Pfizer, and Takeda. Dr. Teixido has received honoraria 
      from Novartis, AstraZeneca, Roche, Merck Sharp Dohme, Pfizer, Janssen, Eli Lilly, 
      and, Bristol Myers Squibb. Dr. Reguart has received honoraria from Amgen, 
      AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer, Guardant, Janssen, Merck 
      Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, and Takeda. Dr. Insa has received 
      honoraria from Roche, Bristol Myers Squibb, Sanofi, Pfizer, Boehringer Ingelheim, 
      AstraZeneca, Takeda, Bayer, Merck Sharp & Dohme, and Eli Lilly. Dr. Mancheno has 
      received honoraria from Roche, AstraZeneca, and Pfizer. Dr. Palanca has received 
      honoraria from Roche Pharma, Pfizer, Amgen, AstraZeneca, Takeda, Eli Lilly, and 
      Janssen. Dr. Juan-Vidal has received honoraria from Boehringer Ingelheim, Bristol 
      Myers Squibb, Merck Sharp & Dohme, Roche/Genetech, AstraZeneca, Pfizer, Eli 
      Lilly, and Takeda. Dr. Baixeras has received honoraria from AstraZeneca and Eli 
      Lilly. Dr. Nadal has received research funding from Roche, Pfizer, Bristol-Myers 
      Squibb and Merck Serono, and honoraria from Roche, Bristol Myers Squibb, Merck 
      Sharp Dohme, Merck Serono, Sanofi, Pfizer, Eli Lilly, Janssen, Amgen, 
      Daiichi-Sankyo, Boehringer Ingelheim, AstraZeneca, Takeda, Sanofi, Pierre Fabre, 
      Qiagen, Janssen, and Bayer. Dr. Calles has received research funding from Merck 
      Sharp & Dome, and honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, 
      Roche/Genentech, Eli Lilly and Company, Novartis, Takeda, Merck Sharp & Dohme, 
      and Bristol Myers Squibb. Dr. Martin has received honoraria from Daiichi-Sankyo 
      and Pfizer. Dr. Salas has received honoraria from Boehringer Ingelheim, Pfizer, 
      and Merck Sharp & Dohme. Dr. Provencio has received honoraria from AstraZeneca, 
      Boehringer Ingelheim, Pfizer, Roche/Genentech, Takeda, Merck Sharp & Dohme, and 
      Bristol Myers Squibb. Dr. Massuti has received research funding from Bristol 
      Myers Squibb, and honoraria from Bristol Myers Squibb, Roche, Janssen, Merck 
      Sharp & Dohme, and AstraZeneca. Dr. Majem has received research funding from 
      10.13039/100002429Amgen Inc., AstraZeneca, Bristol Myers Squibb, and Roche, and 
      honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, 
      Kyowa Kyrin, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, Sanofi, and 
      Takeda. Dr. Paz-Ares has received research funding from Merck Sharp & Dohme, 
      AstraZeneca, Pfizer, and Bristol-Myers Squibb, and honoraria from Eli Lilly, 
      Merck Sharp & Dohme, Roche, Pharmamar, Merck, AstraZeneca, Novartis, Servier, 
      Amgen, Pfizer, Sanofi, Bayer, Bristol-Myers Squibb, Mirati, GlaxoSmithKline, 
      Janssen, Takeda, and Mirati. Dr. Lopez-Rios has received research funding from 
      Eli Lilly, AstraZeneca, Roche, Pfizer, and ThermoFisher Scientific, and honoraria 
      from Abbvie, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, 
      Janssen, Eli Lilly, Merck Sharp & Dohme, Merck, Pfizer, Roche, Sanofi, Takeda, 
      and Thermo Fisher. The remaining authors declare no conflict of interest.
EDAT- 2024/03/25 06:44
MHDA- 2024/03/25 06:45
PMCR- 2024/02/20
CRDT- 2024/03/25 04:40
PHST- 2023/12/05 00:00 [received]
PHST- 2024/01/31 00:00 [revised]
PHST- 2024/02/18 00:00 [accepted]
PHST- 2024/03/25 06:45 [medline]
PHST- 2024/03/25 06:44 [pubmed]
PHST- 2024/03/25 04:40 [entrez]
PHST- 2024/02/20 00:00 [pmc-release]
AID - S2666-3643(24)00023-7 [pii]
AID - 100653 [pii]
AID - 10.1016/j.jtocrr.2024.100653 [doi]
PST - epublish
SO  - JTO Clin Res Rep. 2024 Feb 20;5(4):100653. doi: 10.1016/j.jtocrr.2024.100653. 
      eCollection 2024 Apr.