BACKGROUND: The discovery of distinct subsets of nonsmall cell lung cancer (NSCLC) characterized by activation of driver oncogenes has greatly affected personalized therapy. It is hypothesized that the dominant oncogene in NSCLC would be associated with distinct patterns of metastatic spread in NSCLC at the time of diagnosis. METHODS: A total of 209 consecutive patients with stage IV nonsquamous NSCLC with an EGFR (epidermal growth factor receptor) mutation (N = 39), KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation (N = 49), ALK (anaplastic lymphoma receptor tyrosine kinase) gene rearrangement (N = 41), or wild-type for all 3 (triple negative, N = 80) were included. The percentage of patients with metastatic disease at a given site was compared between each molecular cohort (EGFR, KRAS, or ALK) and the triple negative cohort. RESULTS: ALK gene rearrangement was significantly associated with pericardial disease (odds ratio [OR] = 4.61; 95% confidence interval [CI] = 1.30, 16.37; P = .02) and pleural disease (OR = 4.80; 95% CI = 2.10, 10.97; P < .001). Patients with ALK gene rearrangements (OR = 5.50; 95% CI = 1.76, 17.18; P = .003) and patients with EGFR mutations (OR = 5.17; 95% CI = 1.63, 16.43; P = .006) were predisposed to liver metastasis compared to the triple negative cohort. No molecular cohort had a predisposition to pulmonary nodules, or adrenal, bone, or brain metastasis compared to the triple negative cohort. The mean number of metastatic disease sites in patients within the ALK rearranged cohort was significantly greater than that of the triple negative cohort (mean = 3.6 sites vs 2.5 sites, P < .0001). CONCLUSIONS: The results support the hypothesis that the dominant molecular oncogenes in NSCLC are associated with different biological behaviors manifesting as distinct patterns of metastatic spread at the time of diagnosis.
BACKGROUND: The discovery of distinct subsets of nonsmall cell lung cancer (NSCLC) characterized by activation of driver oncogenes has greatly affected personalized therapy. It is hypothesized that the dominant oncogene in NSCLC would be associated with distinct patterns of metastatic spread in NSCLC at the time of diagnosis. METHODS: A total of 209 consecutive patients with stage IV nonsquamous NSCLC with an EGFR (epidermal growth factor receptor) mutation (N = 39), KRAS (v-Ki-ras2 Kirsten ratsarcoma viral oncogene homolog) mutation (N = 49), ALK (anaplastic lymphoma receptor tyrosine kinase) gene rearrangement (N = 41), or wild-type for all 3 (triple negative, N = 80) were included. The percentage of patients with metastatic disease at a given site was compared between each molecular cohort (EGFR, KRAS, or ALK) and the triple negative cohort. RESULTS:ALK gene rearrangement was significantly associated with pericardial disease (odds ratio [OR] = 4.61; 95% confidence interval [CI] = 1.30, 16.37; P = .02) and pleural disease (OR = 4.80; 95% CI = 2.10, 10.97; P < .001). Patients with ALK gene rearrangements (OR = 5.50; 95% CI = 1.76, 17.18; P = .003) and patients with EGFR mutations (OR = 5.17; 95% CI = 1.63, 16.43; P = .006) were predisposed to liver metastasis compared to the triple negative cohort. No molecular cohort had a predisposition to pulmonary nodules, or adrenal, bone, or brain metastasis compared to the triple negative cohort. The mean number of metastatic disease sites in patients within the ALK rearranged cohort was significantly greater than that of the triple negative cohort (mean = 3.6 sites vs 2.5 sites, P < .0001). CONCLUSIONS: The results support the hypothesis that the dominant molecular oncogenes in NSCLC are associated with different biological behaviors manifesting as distinct patterns of metastatic spread at the time of diagnosis.
Authors: Gregory J Riely; Mark G Kris; Daniel Rosenbaum; Jenifer Marks; Allan Li; Dhananjay A Chitale; Khedoudja Nafa; Elyn R Riedel; Meier Hsu; William Pao; Vincent A Miller; Marc Ladanyi Journal: Clin Cancer Res Date: 2008-09-15 Impact factor: 12.531
Authors: Giorgio Vittorio Scagliotti; Purvish Parikh; Joachim von Pawel; Bonne Biesma; Johan Vansteenkiste; Christian Manegold; Piotr Serwatowski; Ulrich Gatzemeier; Raghunadharao Digumarti; Mauro Zukin; Jin S Lee; Anders Mellemgaard; Keunchil Park; Shehkar Patil; Janusz Rolski; Tuncay Goksel; Filippo de Marinis; Lorinda Simms; Katherine P Sugarman; David Gandara Journal: J Clin Oncol Date: 2008-05-27 Impact factor: 44.544
Authors: Li Ding; Gad Getz; David A Wheeler; Elaine R Mardis; Michael D McLellan; Kristian Cibulskis; Carrie Sougnez; Heidi Greulich; Donna M Muzny; Margaret B Morgan; Lucinda Fulton; Robert S Fulton; Qunyuan Zhang; Michael C Wendl; Michael S Lawrence; David E Larson; Ken Chen; David J Dooling; Aniko Sabo; Alicia C Hawes; Hua Shen; Shalini N Jhangiani; Lora R Lewis; Otis Hall; Yiming Zhu; Tittu Mathew; Yanru Ren; Jiqiang Yao; Steven E Scherer; Kerstin Clerc; Ginger A Metcalf; Brian Ng; Aleksandar Milosavljevic; Manuel L Gonzalez-Garay; John R Osborne; Rick Meyer; Xiaoqi Shi; Yuzhu Tang; Daniel C Koboldt; Ling Lin; Rachel Abbott; Tracie L Miner; Craig Pohl; Ginger Fewell; Carrie Haipek; Heather Schmidt; Brian H Dunford-Shore; Aldi Kraja; Seth D Crosby; Christopher S Sawyer; Tammi Vickery; Sacha Sander; Jody Robinson; Wendy Winckler; Jennifer Baldwin; Lucian R Chirieac; Amit Dutt; Tim Fennell; Megan Hanna; Bruce E Johnson; Robert C Onofrio; Roman K Thomas; Giovanni Tonon; Barbara A Weir; Xiaojun Zhao; Liuda Ziaugra; Michael C Zody; Thomas Giordano; Mark B Orringer; Jack A Roth; Margaret R Spitz; Ignacio I Wistuba; Bradley Ozenberger; Peter J Good; Andrew C Chang; David G Beer; Mark A Watson; Marc Ladanyi; Stephen Broderick; Akihiko Yoshizawa; William D Travis; William Pao; Michael A Province; George M Weinstock; Harold E Varmus; Stacey B Gabriel; Eric S Lander; Richard A Gibbs; Matthew Meyerson; Richard K Wilson Journal: Nature Date: 2008-10-23 Impact factor: 49.962
Authors: S Michael Rothenberg; Jeffrey A Engelman; Sheila Le; David J Riese; Daniel A Haber; Jeffrey Settleman Journal: Proc Natl Acad Sci U S A Date: 2008-08-18 Impact factor: 11.205
Authors: Gaorav P Gupta; Don X Nguyen; Anne C Chiang; Paula D Bos; Juliet Y Kim; Cristina Nadal; Roger R Gomis; Katia Manova-Todorova; Joan Massagué Journal: Nature Date: 2007-04-12 Impact factor: 49.962
Authors: Taofeek K Owonikoko; Jack Arbiser; Amelia Zelnak; Hui-Kuo G Shu; Hyunsuk Shim; Adam M Robin; Steven N Kalkanis; Timothy G Whitsett; Bodour Salhia; Nhan L Tran; Timothy Ryken; Michael K Moore; Kathleen M Egan; Jeffrey J Olson Journal: Nat Rev Clin Oncol Date: 2014-02-25 Impact factor: 66.675