%0 Journal Article %1 jee2022overall %A Jee, Justin %A Lebow, Emily S %A Yeh, Randy %A Das, Jeeban P %A Namakydoust, Azadeh %A Paik, Paul K %A Chaft, Jamie E %A Jayakumaran, Gowtham %A Rose Brannon, A %A Benayed, Ryma %A Zehir, Ahmet %A Donoghue, Mark %A Schultz, Nikolaus %A Chakravarty, Debyani %A Kundra, Ritika %A Madupuri, Ramyasree %A Murciano-Goroff, Yonina R %A Tu, Hai-Yan %A Xu, Chong-Rui %A Martinez, Andrés %A Wilhelm, Clare %A Galle, Jesse %A Daly, Bobby %A Yu, Helena A %A Offin, Michael %A Hellmann, Matthew D %A Lito, Piro %A Arbour, Kathryn C %A Zauderer, Marjorie G %A Kris, Mark G %A Ng, Kenneth K %A Eng, Juliana %A Preeshagul, Isabel %A Victoria Lai, W %A Fiore, John J %A Iqbal, Afsheen %A Molena, Daniela %A Rocco, Gaetano %A Park, Bernard J %A Lim, Lee P %A Li, Mark %A Tong-Li, Candace %A De Silva, Madhawa %A Chan, David L %A Diakos, Connie I %A Itchins, Malinda %A Clarke, Stephen %A Pavlakis, Nick %A Lee, Adrian %A Rekhtman, Natasha %A Chang, Jason %A Travis, William D %A Riely, Gregory J %A Solit, David B %A Gonen, Mithat %A Rusch, Valerie W %A Rimner, Andreas %A Gomez, Daniel %A Drilon, Alexander %A Scher, Howard I %A Shah, Sohrab P %A Berger, Michael F %A Arcila, Maria E %A Ladanyi, Marc %A Levine, Ross L %A Shen, Ronglai %A Razavi, Pedram %A Reis-Filho, Jorge S %A Jones, David R %A Rudin, Charles M %A Isbell, James M %A Li, Bob T %C United States %D 2022 %J Nature medicine %K 92c32-pathology-pathophysiology 92c40-biochemistry-molecular-biology 92c60-medical-epidemiology %N 11 %P 2353--2363 %R 10.1038/s41591-022-02047-z %T Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer %U https://pubmed.ncbi.nlm.nih.gov/36357680 %V 28 %X Circulating tumor DNA (ctDNA) sequencing guides therapy decisions but has been studied mostly in small cohorts without sufficient follow-up to determine its influence on overall survival. We prospectively followed an international cohort of 1,127 patients with non-small-cell lung cancer and ctDNA-guided therapy. ctDNA detection was associated with shorter survival (hazard ratio (HR), 2.05; 95% confidence interval (CI), 1.74-2.42; P < 0.001) independently of clinicopathologic features and metabolic tumor volume. Among the 722 (64%) patients with detectable ctDNA, 255 (23%) matched to targeted therapy by ctDNA sequencing had longer survival than those not treated with targeted therapy (HR, 0.63; 95% CI, 0.52-0.76; P < 0.001). Genomic alterations in ctDNA not detected by time-matched tissue sequencing were found in 25% of the patients. These ctDNA-only alterations disproportionately featured subclonal drivers of resistance, including RICTOR and PIK3CA alterations, and were associated with short survival. Minimally invasive ctDNA profiling can identify heterogeneous drivers not captured in tissue sequencing and expand community access to life-prolonging therapy.

@article{jee2022overall, abstract = {Circulating tumor DNA (ctDNA) sequencing guides therapy decisions but has been studied mostly in small cohorts without sufficient follow-up to determine its influence on overall survival. We prospectively followed an international cohort of 1,127 patients with non-small-cell lung cancer and ctDNA-guided therapy. ctDNA detection was associated with shorter survival (hazard ratio (HR), 2.05; 95% confidence interval (CI), 1.74-2.42; P < 0.001) independently of clinicopathologic features and metabolic tumor volume. Among the 722 (64%) patients with detectable ctDNA, 255 (23%) matched to targeted therapy by ctDNA sequencing had longer survival than those not treated with targeted therapy (HR, 0.63; 95% CI, 0.52-0.76; P < 0.001). Genomic alterations in ctDNA not detected by time-matched tissue sequencing were found in 25% of the patients. These ctDNA-only alterations disproportionately featured subclonal drivers of resistance, including RICTOR and PIK3CA alterations, and were associated with short survival. Minimally invasive ctDNA profiling can identify heterogeneous drivers not captured in tissue sequencing and expand community access to life-prolonging therapy.}, added-at = {2024-03-08T03:03:42.000+0100}, address = {United States}, author = {Jee, Justin and Lebow, Emily S and Yeh, Randy and Das, Jeeban P and Namakydoust, Azadeh and Paik, Paul K and Chaft, Jamie E and Jayakumaran, Gowtham and Rose Brannon, A and Benayed, Ryma and Zehir, Ahmet and Donoghue, Mark and Schultz, Nikolaus and Chakravarty, Debyani and Kundra, Ritika and Madupuri, Ramyasree and Murciano-Goroff, Yonina R and Tu, Hai-Yan and Xu, Chong-Rui and Martinez, Andrés and Wilhelm, Clare and Galle, Jesse and Daly, Bobby and Yu, Helena A and Offin, Michael and Hellmann, Matthew D and Lito, Piro and Arbour, Kathryn C and Zauderer, Marjorie G and Kris, Mark G and Ng, Kenneth K and Eng, Juliana and Preeshagul, Isabel and Victoria Lai, W and Fiore, John J and Iqbal, Afsheen and Molena, Daniela and Rocco, Gaetano and Park, Bernard J and Lim, Lee P and Li, Mark and Tong-Li, Candace and De Silva, Madhawa and Chan, David L and Diakos, Connie I and Itchins, Malinda and Clarke, Stephen and Pavlakis, Nick and Lee, Adrian and Rekhtman, Natasha and Chang, Jason and Travis, William D and Riely, Gregory J and Solit, David B and Gonen, Mithat and Rusch, Valerie W and Rimner, Andreas and Gomez, Daniel and Drilon, Alexander and Scher, Howard I and Shah, Sohrab P and Berger, Michael F and Arcila, Maria E and Ladanyi, Marc and Levine, Ross L and Shen, Ronglai and Razavi, Pedram and Reis-Filho, Jorge S and Jones, David R and Rudin, Charles M and Isbell, James M and Li, Bob T}, biburl = {https://www.bibsonomy.org/bibtex/205fcc78863a6a21e0d997c112cceab6f/gdmcbain}, comment = {36357680[pmid] PMC10338177[pmcid]}, doi = {10.1038/s41591-022-02047-z}, interhash = {56c8965b5b322c5d8efd51d4b5fa163c}, intrahash = {05fcc78863a6a21e0d997c112cceab6f}, issn = {10788956}, journal = {Nature medicine}, keywords = {92c32-pathology-pathophysiology 92c40-biochemistry-molecular-biology 92c60-medical-epidemiology}, month = nov, number = 11, pages = {2353--2363}, timestamp = {2024-03-08T03:03:42.000+0100}, title = {Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer}, url = {https://pubmed.ncbi.nlm.nih.gov/36357680}, volume = 28, year = 2022 }