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DOI 10.1038/s41591-022-02047-z

Медицинская библиотека · Nature medicine · 2022

Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer.

Jee Justin, Lebow Emily S, Yeh Randy, Das Jeeban P, Namakydoust Azadeh, Paik Paul K, Chaft Jamie E, Jayakumaran Gowtham, Rose Brannon A, Benayed Ryma, Zehir Ahmet, Donoghue Mark, Schultz Nikolaus, Chakravarty Debyani, Kundra Ritika, Madupuri Ramyasree, Murciano-Goroff Yonina R, Tu Hai-Yan, Xu Chong-Rui, Martinez Andrés, Wilhelm Clare, Galle Jesse, Daly Bobby, Yu Helena A, Offin Michael, Hellmann Matthew D, Lito Piro, Arbour Kathryn C, Zauderer Marjorie G, Kris Mark G, Ng Kenneth K, Eng Juliana, Preeshagul Isabel, Victoria Lai W, Fiore John J, Iqbal Afsheen, Molena Daniela, Rocco Gaetano, Park Bernard J, Lim Lee P, Li Mark, Tong-Li Candace, De Silva Madhawa, Chan David L, Diakos Connie I, Itchins Malinda, Clarke Stephen, Pavlakis Nick, Lee Adrian, Rekhtman Natasha, Chang Jason, Travis William D, Riely Gregory J, Solit David B, Gonen Mithat, Rusch Valerie W, Rimner Andreas, Gomez Daniel, Drilon Alexander, Scher Howard I, Shah Sohrab P, Berger Michael F, Arcila Maria E, Ladanyi Marc, Levine Ross L, Shen Ronglai, Razavi Pedram, Reis-Filho Jorge S, Jones David R, Rudin Charles M, Isbell James M, Li Bob T

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод пока не подготовлен

Аннотация

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.

Для цитирования: Jee Justin, Lebow Emily S, Yeh Randy, Das Jeeban P, Namakydoust Azadeh, Paik Paul K, Chaft Jamie E, Jayakumaran Gowtham, Rose Brannon A, Benayed Ryma, Zehir Ahmet, Donoghue Mark, Schultz Nikolaus, Chakravarty Debyani, Kundra Ritika, Madupuri Ramyasree, Murciano-Goroff Yonina R, Tu Hai-Yan, Xu Chong-Rui, Martinez Andrés, Wilhelm Clare, Galle Jesse, Daly Bobby, Yu Helena A, Offin Michael, Hellmann Matthew D, Lito Piro, Arbour Kathryn C, Zauderer Marjorie G, Kris Mark G, Ng Kenneth K, Eng Juliana, Preeshagul Isabel, Victoria Lai W, Fiore John J, Iqbal Afsheen, Molena Daniela, Rocco Gaetano, Park Bernard J, Lim Lee P, Li Mark, Tong-Li Candace, De Silva Madhawa, Chan David L, Diakos Connie I, Itchins Malinda, Clarke Stephen, Pavlakis Nick, Lee Adrian, Rekhtman Natasha, Chang Jason, Travis William D, Riely Gregory J, Solit David B, Gonen Mithat, Rusch Valerie W, Rimner Andreas, Gomez Daniel, Drilon Alexander, Scher Howard I, Shah Sohrab P, Berger Michael F, Arcila Maria E, Ladanyi Marc, Levine Ross L, Shen Ronglai, Razavi Pedram, Reis-Filho Jorge S, Jones David R, Rudin Charles M, Isbell James M, Li Bob T. Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer.. Nature medicine. 2022. DOI: 10.1038/s41591-022-02047-z.

Предметные рубрики MeSH

HumansCirculating Tumor DNACarcinoma, Non-Small-Cell LungLung NeoplasmsBiomarkers, TumorMutationHigh-Throughput Nucleotide Sequencing
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