Francesco Facchinetti1, Maria Virginia Bluthgen2, Gabrielle Tergemina-Clain3, Laura Faivre4, Jean-Pierre Pignon5, David Planchard6, Jordi Remon7, Jean-Charles Soria8, Ludovic Lacroix9, Benjamin Besse10. 1. Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France; INSERM U981, Gustave Roussy Cancer Campus, Villejuif, France; Medical Oncology Unit, University Hospital of Parma, Parma, Italy. Electronic address: Francesco.FACCHINETTI@gustaveroussy.fr. 2. Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: mvbluthgen@gmail.com. 3. Service de Biostatistique et Epidémiologie, Gustave Roussy Cancer Campus and INSERM U1018, Université Paris-Saclay, Villejuif, France. Electronic address: gabrielle.clain@gmail.com. 4. Service de Biostatistique et Epidémiologie, Gustave Roussy Cancer Campus and INSERM U1018, Université Paris-Saclay, Villejuif, France. Electronic address: laura4.faivre@gmail.com. 5. Service de Biostatistique et Epidémiologie, Gustave Roussy Cancer Campus and INSERM U1018, Université Paris-Saclay, Villejuif, France. Electronic address: Jean-Pierre.PIGNON@gustaveroussy.fr. 6. Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: David.PLANCHARD@gustaveroussy.fr. 7. Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: jremon@vhio.net. 8. INSERM U981, Gustave Roussy Cancer Campus, Villejuif, France; Drug Development Department, Gustave Roussy Cancer Campus, Villejuif, France; University Paris-Sud Kremlin Bicetre/Chatenay-Malabry, Le Kremlin-Bicêtre, France. Electronic address: Jean-Charles.SORIA@gustaveroussy.fr. 9. University Paris-Sud Kremlin Bicetre/Chatenay-Malabry, Le Kremlin-Bicêtre, France; Medical Biology and Pathology, Gustave Roussy Cancer Campus, Villejuif, France; Genomic platform, Molecular Biopathology Unit and Biological Resource Center, AMMICA, INSERM US23/CNRS UMS3655, University Paris XI, Gustave Roussy, Villejuif, France. Electronic address: Ludovic.LACROIX@gustaveroussy.fr. 10. Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France; University Paris-Sud Kremlin Bicetre/Chatenay-Malabry, Le Kremlin-Bicêtre, France. Electronic address: Benjamin.Besse@gustaveroussy.fr.
Abstract
BACKGROUND: LKB1/STK11 (STK11) is among the most inactivated tumor-suppressor genes in non-small cell lung cancer (NSCLC). While evidence concerning the biologic role of STK11 is accumulating, its prognostic significance in advanced NSCLC has not been envisaged yet. MATERIALS AND METHODS: This retrospective analysis included consecutive NSCLC patients with available STK11 information who underwent a platinum-based chemotherapy. STK11 mutational status was correlated to clinico-pathological and mutational features. Kaplan-Meier and Cox models were used for survival curves and multivariate analyses, respectively. RESULTS: Among the 302 patients included, 267 (89%) were diagnosed with stage IIIB/IV NSCLC and 25 (8%) harbored a STK11 mutation (STK11mut). No statistical differences were observed between STK11 status and clinico-pathological variables. We detected a significant correlation between STK11 and KRAS status (p=0.008); among the 25 STK11mut patients, 13 (52%) harbored a concomitant KRAS mutation. Overall survival (OS) was shorter for STK11mut (median OS=10.4months) compared to wild-type patients (STK11wt; median OS=17.3months) in univariate analysis (p=0.085). STK11 status did not impact upon OS in multivariate analysis (p=0.45) and non-significant results were observed for progression-free survival. The co-occurrence of KRAS and STK11 mutations suggest a trend toward detrimental effect in OS (p=0.12). CONCLUSIONS: In our cohort enriched for advanced NSCLC patients who received platinum-based chemotherapy, STK11 mutations were not specifically associated with clinico-pathological features and they did not impact upon survival. We confirm the positive correlation between STK11 and KRAS mutations. The co-occurrence of KRAS and STK11 mutations could label a more aggressive molecular subtype of NSCLC.
BACKGROUND:LKB1/STK11 (STK11) is among the most inactivated tumor-suppressor genes in non-small cell lung cancer (NSCLC). While evidence concerning the biologic role of STK11 is accumulating, its prognostic significance in advanced NSCLC has not been envisaged yet. MATERIALS AND METHODS: This retrospective analysis included consecutive NSCLCpatients with available STK11 information who underwent a platinum-based chemotherapy. STK11 mutational status was correlated to clinico-pathological and mutational features. Kaplan-Meier and Cox models were used for survival curves and multivariate analyses, respectively. RESULTS: Among the 302 patients included, 267 (89%) were diagnosed with stage IIIB/IV NSCLC and 25 (8%) harbored a STK11 mutation (STK11mut). No statistical differences were observed between STK11 status and clinico-pathological variables. We detected a significant correlation between STK11 and KRAS status (p=0.008); among the 25 STK11mut patients, 13 (52%) harbored a concomitant KRAS mutation. Overall survival (OS) was shorter for STK11mut (median OS=10.4months) compared to wild-type patients (STK11wt; median OS=17.3months) in univariate analysis (p=0.085). STK11 status did not impact upon OS in multivariate analysis (p=0.45) and non-significant results were observed for progression-free survival. The co-occurrence of KRAS and STK11 mutations suggest a trend toward detrimental effect in OS (p=0.12). CONCLUSIONS: In our cohort enriched for advanced NSCLCpatients who received platinum-based chemotherapy, STK11 mutations were not specifically associated with clinico-pathological features and they did not impact upon survival. We confirm the positive correlation between STK11 and KRAS mutations. The co-occurrence of KRAS and STK11 mutations could label a more aggressive molecular subtype of NSCLC.
Authors: Rocio Perez-Johnston; Jose A Araujo-Filho; James G Connolly; Raul Caso; Karissa Whiting; Kay See Tan; Jian Zhou; Peter Gibbs; Natasha Rekhtman; Michelle S Ginsberg; David R Jones Journal: Radiology Date: 2022-03-01 Impact factor: 29.146
Authors: Ferdinandos Skoulidis; Michael E Goldberg; Danielle M Greenawalt; Matthew D Hellmann; Mark M Awad; Justin F Gainor; Alexa B Schrock; Ryan J Hartmaier; Sally E Trabucco; Laurie Gay; Siraj M Ali; Julia A Elvin; Gaurav Singal; Jeffrey S Ross; David Fabrizio; Peter M Szabo; Han Chang; Ariella Sasson; Sujaya Srinivasan; Stefan Kirov; Joseph Szustakowski; Patrik Vitazka; Robin Edwards; Jose A Bufill; Neelesh Sharma; Sai-Hong I Ou; Nir Peled; David R Spigel; Hira Rizvi; Elizabeth Jimenez Aguilar; Brett W Carter; Jeremy Erasmus; Darragh F Halpenny; Andrew J Plodkowski; Niamh M Long; Mizuki Nishino; Warren L Denning; Ana Galan-Cobo; Haifa Hamdi; Taghreed Hirz; Pan Tong; Jing Wang; Jaime Rodriguez-Canales; Pamela A Villalobos; Edwin R Parra; Neda Kalhor; Lynette M Sholl; Jennifer L Sauter; Achim A Jungbluth; Mari Mino-Kenudson; Roxana Azimi; Yasir Y Elamin; Jianjun Zhang; Giulia C Leonardi; Fei Jiang; Kwok-Kin Wong; J Jack Lee; Vassiliki A Papadimitrakopoulou; Ignacio I Wistuba; Vincent A Miller; Garrett M Frampton; Jedd D Wolchok; Alice T Shaw; Pasi A Jänne; Philip J Stephens; Charles M Rudin; William J Geese; Lee A Albacker; John V Heymach Journal: Cancer Discov Date: 2018-05-17 Impact factor: 39.397
Authors: Jacqueline V Aredo; Sukhmani K Padda; Christian A Kunder; Summer S Han; Joel W Neal; Joseph B Shrager; Heather A Wakelee Journal: Lung Cancer Date: 2019-05-15 Impact factor: 6.081