STK11 Inactivation Predicts Rapid Recurrence in Inoperable Early-Stage Non-Small-Cell Lung Cancer
PURPOSE: Molecular factors predicting relapse in early-stage non-small-cell lung cancer (ES-NSCLC) are poorly understood, especially in inoperable patients receiving radiotherapy (RT). In this study, we compared the genomic profiles of inoperable and operable ES-NSCLC.
MATERIALS AND METHODS: This retrospective study included 53 patients with nonsquamous ES-NSCLC (stage I-II) treated at a single institution (University of Chicago) with surgery (ie, operable; n = 30) or RT (ie, inoperable; n = 23) who underwent tumor genomic profiling. A second cohort of ES-NSCLC treated with RT (Stanford, n = 39) was included to power clinical analyses. Prognostic gene alterations were identified and correlated with clinical variables. The primary clinical end point was the correlation of prognostic genes with the cumulative incidence of relapse, disease-free survival, and overall survival (OS) in a pooled RT cohort from the two institutions (N = 62).
RESULTS: Although the surgery cohort exhibited lower rates of relapse, the RT cohort was highly enriched for somatic STK11 mutations (43% v 6.7%). Receiving supplemental oxygen (odds ratio [OR] = 5.5), 20+ pack-years of tobacco smoking (OR = 6.1), and Black race (OR = 4.3) were associated with increased frequency of STK11 mutations. In the pooled RT cohort (N = 62), STK11 mutation was strongly associated with inferior oncologic outcomes: 2-year incidence of relapse was 62% versus 20% and 2-year OS was 52% versus 85%, remaining independently prognostic on multivariable analyses (relapse: subdistribution hazard ratio = 4.0, P = .0041; disease-free survival: hazard ratio, 6.8, P = .0002; OS: hazard ratio, 6.0, P = .022). STK11 mutations were predominantly associated with distant failure, rather than local.
CONCLUSION: In this cohort of ES-NSCLC, STK11 inactivation was associated with poor oncologic outcomes after RT and demonstrated a novel association with clinical hypoxia, which may underlie its correlation with medical inoperability. Further validation in larger cohorts and investigation of effective adjuvant systemic therapies may be warranted.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
|---|---|
| Enthalten in: |
JCO precision oncology - 7(2023) vom: 01. Jan., Seite e2200273 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Katipally, Rohan R [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
AMP-Activated Protein Kinase Kinases |
|---|
| Anmerkungen: |
Date Completed 09.01.2023 Date Revised 01.03.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1200/PO.22.00273 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM351143289 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM351143289 | ||
| 003 | DE-627 | ||
| 005 | 20240301231924.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1200/PO.22.00273 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1313.xml |
| 035 | |a (DE-627)NLM351143289 | ||
| 035 | |a (NLM)36603171 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Katipally, Rohan R |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a STK11 Inactivation Predicts Rapid Recurrence in Inoperable Early-Stage Non-Small-Cell Lung Cancer |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 09.01.2023 | ||
| 500 | |a Date Revised 01.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: Molecular factors predicting relapse in early-stage non-small-cell lung cancer (ES-NSCLC) are poorly understood, especially in inoperable patients receiving radiotherapy (RT). In this study, we compared the genomic profiles of inoperable and operable ES-NSCLC | ||
| 520 | |a MATERIALS AND METHODS: This retrospective study included 53 patients with nonsquamous ES-NSCLC (stage I-II) treated at a single institution (University of Chicago) with surgery (ie, operable; n = 30) or RT (ie, inoperable; n = 23) who underwent tumor genomic profiling. A second cohort of ES-NSCLC treated with RT (Stanford, n = 39) was included to power clinical analyses. Prognostic gene alterations were identified and correlated with clinical variables. The primary clinical end point was the correlation of prognostic genes with the cumulative incidence of relapse, disease-free survival, and overall survival (OS) in a pooled RT cohort from the two institutions (N = 62) | ||
| 520 | |a RESULTS: Although the surgery cohort exhibited lower rates of relapse, the RT cohort was highly enriched for somatic STK11 mutations (43% v 6.7%). Receiving supplemental oxygen (odds ratio [OR] = 5.5), 20+ pack-years of tobacco smoking (OR = 6.1), and Black race (OR = 4.3) were associated with increased frequency of STK11 mutations. In the pooled RT cohort (N = 62), STK11 mutation was strongly associated with inferior oncologic outcomes: 2-year incidence of relapse was 62% versus 20% and 2-year OS was 52% versus 85%, remaining independently prognostic on multivariable analyses (relapse: subdistribution hazard ratio = 4.0, P = .0041; disease-free survival: hazard ratio, 6.8, P = .0002; OS: hazard ratio, 6.0, P = .022). STK11 mutations were predominantly associated with distant failure, rather than local | ||
| 520 | |a CONCLUSION: In this cohort of ES-NSCLC, STK11 inactivation was associated with poor oncologic outcomes after RT and demonstrated a novel association with clinical hypoxia, which may underlie its correlation with medical inoperability. Further validation in larger cohorts and investigation of effective adjuvant systemic therapies may be warranted | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a STK11 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a AMP-Activated Protein Kinase Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.3 |2 NLM | |
| 700 | 1 | |a Spurr, Liam F |e verfasserin |4 aut | |
| 700 | 1 | |a Gutiontov, Stanley I |e verfasserin |4 aut | |
| 700 | 1 | |a Turchan, William Tyler |e verfasserin |4 aut | |
| 700 | 1 | |a Connell, Philip |e verfasserin |4 aut | |
| 700 | 1 | |a Juloori, Aditya |e verfasserin |4 aut | |
| 700 | 1 | |a Malik, Renuka |e verfasserin |4 aut | |
| 700 | 1 | |a Binkley, Michael S |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Alice L |e verfasserin |4 aut | |
| 700 | 1 | |a Rouhani, Sherin J |e verfasserin |4 aut | |
| 700 | 1 | |a Chervin, Carolina Soto |e verfasserin |4 aut | |
| 700 | 1 | |a Wanjari, Pankhuri |e verfasserin |4 aut | |
| 700 | 1 | |a Segal, Jeremy P |e verfasserin |4 aut | |
| 700 | 1 | |a Ng, Victor |e verfasserin |4 aut | |
| 700 | 1 | |a Loo, Billy W |e verfasserin |4 aut | |
| 700 | 1 | |a Gomez, Daniel R |e verfasserin |4 aut | |
| 700 | 1 | |a Bestvina, Christine M |e verfasserin |4 aut | |
| 700 | 1 | |a Vokes, Everett E |e verfasserin |4 aut | |
| 700 | 1 | |a Ferguson, Mark K |e verfasserin |4 aut | |
| 700 | 1 | |a Donington, Jessica S |e verfasserin |4 aut | |
| 700 | 1 | |a Diehn, Maximilian |e verfasserin |4 aut | |
| 700 | 1 | |a Pitroda, Sean P |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t JCO precision oncology |d 2017 |g 7(2023) vom: 01. Jan., Seite e2200273 |w (DE-627)NLM273576054 |x 2473-4284 |7 nnns |
| 773 | 1 | 8 | |g volume:7 |g year:2023 |g day:01 |g month:01 |g pages:e2200273 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1200/PO.22.00273 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 7 |j 2023 |b 01 |c 01 |h e2200273 | ||