Jacob M Sands1, Tom Nguyen2, Priyanka Shivdasani3, Adrian G Sacher4, Michael L Cheng4, Ryan S Alden2, Pasi A Jänne4, Frank C Kuo3, Geoffrey R Oxnard4, Lynette M Sholl3. 1. Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA; Department of Medicine, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA. Electronic address: jacob_sands@dfci.harvard.edu. 2. Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA. 3. Department of Pathology, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA. 4. Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA; Department of Medicine, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA.
Abstract
OBJECTIVES: Potentially targetable genomic alterations have been identified in lung squamous cell carcinoma (LUSC), but none have yet translated into effective therapy. We examined potential benefits of next generation sequencing (NGS) in a cohort of consecutive LUSC patients with emphasis on distinctions between smokers and light/never smokers and implications for clinical trial enrollment. METHODS: We retrospectively evaluated results from an internally developed NGS assay (OncoPanel) targeting ∼300 genes with a mean overall target coverage of >200x for consecutive LUSC seen at our institution over 30 months. RESULTS: Tissue was obtained from 172 patients for targeted NGS. 42 (24 %) samples were insufficient for testing. Median age of tested patients was 66, including 87 % moderate/heavy versus 13 % light/never smokers; 66 % were stage IIIB or IV. Of 130 patients with evaluable NGS results, 49 (38 %) had at least 1 alteration qualifying for enrollment to a LungMAP treatment arm (PIK3CA, MET, FGFR family, cell cycle, or homologous recombination pathways) or for an approved therapy or other clinical trial (e.g. EGFR sensitizing mutations, MET exon 14 splice mutations, TSC1/2 mutation, or microsatellite instability). Therapeutic targets were enriched in light/never smokers (47 % vs 35 % moderate/heavy smokers). Unexpectedly, genomic features suggested an alternative diagnosis (metastatic cutaneous squamous carcinoma; mesothelioma) in 7 patients, including 35 % of never/light smokers. CONCLUSION: NGS in a real-world LUSC cohort yields potentially targetable genomic alterations informing clinical trial enrollment and approved therapies and critical diagnostic insights. Our findings strongly support current guidelines recommending mutational profiling of LUSC arising in light/never smoking patients; the utility of sequencing in smokers with LUSC appears to be limited to identification of research targets.
OBJECTIVES: Potentially targetable genomic alterations have been identified in lung squamous cell carcinoma (LUSC), but none have yet translated into effective therapy. We examined potential benefits of next generation sequencing (NGS) in a cohort of consecutive LUSCpatients with emphasis on distinctions between smokers and light/never smokers and implications for clinical trial enrollment. METHODS: We retrospectively evaluated results from an internally developed NGS assay (OncoPanel) targeting ∼300 genes with a mean overall target coverage of >200x for consecutive LUSC seen at our institution over 30 months. RESULTS: Tissue was obtained from 172 patients for targeted NGS. 42 (24 %) samples were insufficient for testing. Median age of tested patients was 66, including 87 % moderate/heavy versus 13 % light/never smokers; 66 % were stage IIIB or IV. Of 130 patients with evaluable NGS results, 49 (38 %) had at least 1 alteration qualifying for enrollment to a LungMAP treatment arm (PIK3CA, MET, FGFR family, cell cycle, or homologous recombination pathways) or for an approved therapy or other clinical trial (e.g. EGFR sensitizing mutations, MET exon 14 splice mutations, TSC1/2 mutation, or microsatellite instability). Therapeutic targets were enriched in light/never smokers (47 % vs 35 % moderate/heavy smokers). Unexpectedly, genomic features suggested an alternative diagnosis (metastatic cutaneous squamous carcinoma; mesothelioma) in 7 patients, including 35 % of never/light smokers. CONCLUSION: NGS in a real-world LUSC cohort yields potentially targetable genomic alterations informing clinical trial enrollment and approved therapies and critical diagnostic insights. Our findings strongly support current guidelines recommending mutational profiling of LUSC arising in light/never smoking patients; the utility of sequencing in smokers with LUSC appears to be limited to identification of research targets.
Authors: Gina M Castellano; Saman Zeeshan; Olga B Garbuzenko; Hatim E Sabaawy; Jyoti Malhotra; Tamara Minko; Sharon R Pine Journal: Mol Cancer Ther Date: 2022-09-06 Impact factor: 6.009
Authors: Elio Adib; Amin H Nassar; Sarah Abou Alaiwi; Stefan Groha; Elie W Akl; Lynette M Sholl; Kesi S Michael; Mark M Awad; Pasi A Jӓnne; Alexander Gusev; David J Kwiatkowski Journal: Genome Med Date: 2022-04-15 Impact factor: 15.266
Authors: Bart Koopman; Birgitta I Hiddinga; Inge Platteel; Joost L Kluiver; Wim Timens; André B Mulder; Jaap A van Doesum; Ed Schuuring; Arjan Diepstra; Léon C van Kempen Journal: Histopathology Date: 2021-04-03 Impact factor: 7.778