The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases

Paul W. Sperduto, T. Jonathan Yang, Kathryn Beal, Hubert Pan, Paul D. Brown, Ananta Bangdiwala, Ryan Shanley, Norman Yeh, Laurie E. Gaspar, Steve Braunstein, Penny Sneed, John Boyle, John P. Kirkpatrick, Kimberley S. Mak, Helen A. Shih, Alex Engelman, David Roberge, Nils D. Arvold, Brian Alexander, Mark M. AwadJoseph Contessa, Veronica Chiang, John Hardie, Daniel Ma, Emil Lou, William Sperduto, Minesh P. Mehta

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Purpose Lung cancer remains the most common cause of both cancer mortality and brain metastases (BM). The purpose of this study was to assess the effect of gene alterations and tyrosine kinase inhibition (TKI) on median survival (MS) and cause of death (CoD) in patients with BM from lung adenocarcinoma (L-adeno). Methods A multi-institutional retrospective database of patients with L-adeno and newly diagnosed BM between 2006 and 2014 was created. Demographics, gene alterations, treatment, MS, and CoD were analyzed. The treatment patterns and outcomes were compared with those in prior trials. Results Of 1521 L-adeno patients, 816 (54%) had known alteration status. The gene alteration rates were 29%, 10%, and 26% for EGFR, ALK, and KRAS, respectively. The time from primary diagnosis to BM for EGFR−/+ was 10/15 months (P=.02) and for ALK−/+ was 10/20 months (P<.01), respectively. The MS for the group overall (n=1521) was 15 months. The MS from first treatment for BM for EGFR and ALK−, EGFR+, ALK+ were 14, 23 (P<.01), and 45 (P<.0001) months, respectively. The MS after BM for EGFR+ patients who did/did not receive TKI before BM was 17/30 months (P<.01), respectively, but the risk of death was not statistically different between TKI-naïve patients who did/did not receive TKI after the diagnosis of BM (EGFR/ALK hazard ratios: 1.06 [P=.84]/1.60 [P=.45], respectively). The CoD was nonneurologic in 82% of patients with known CoD. Conclusion EGFR and ALK gene alterations are associated with delayed onset of BM and longer MS relative to patients without these alterations. The CoD was overwhelmingly nonneurologic in patients with known CoD.

Original languageEnglish (US)
Pages (from-to)406-413
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume96
Issue number2
DOIs
StatePublished - Oct 1 2016

Fingerprint

tyrosine
metastasis
death
genes
Protein-Tyrosine Kinases
lungs
brain
Cause of Death
Neoplasm Metastasis
Survival
causes
Brain
Genes
cancer
erbB-1 Genes
Adenocarcinoma of lung
mortality
Brain Neoplasms
hazards
Lung Neoplasms

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases. / Sperduto, Paul W.; Yang, T. Jonathan; Beal, Kathryn; Pan, Hubert; Brown, Paul D.; Bangdiwala, Ananta; Shanley, Ryan; Yeh, Norman; Gaspar, Laurie E.; Braunstein, Steve; Sneed, Penny; Boyle, John; Kirkpatrick, John P.; Mak, Kimberley S.; Shih, Helen A.; Engelman, Alex; Roberge, David; Arvold, Nils D.; Alexander, Brian; Awad, Mark M.; Contessa, Joseph; Chiang, Veronica; Hardie, John; Ma, Daniel; Lou, Emil; Sperduto, William; Mehta, Minesh P.

In: International Journal of Radiation Oncology Biology Physics, Vol. 96, No. 2, 01.10.2016, p. 406-413.

Research output: Contribution to journalArticle

Sperduto, PW, Yang, TJ, Beal, K, Pan, H, Brown, PD, Bangdiwala, A, Shanley, R, Yeh, N, Gaspar, LE, Braunstein, S, Sneed, P, Boyle, J, Kirkpatrick, JP, Mak, KS, Shih, HA, Engelman, A, Roberge, D, Arvold, ND, Alexander, B, Awad, MM, Contessa, J, Chiang, V, Hardie, J, Ma, D, Lou, E, Sperduto, W & Mehta, MP 2016, 'The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases', International Journal of Radiation Oncology Biology Physics, vol. 96, no. 2, pp. 406-413. https://doi.org/10.1016/j.ijrobp.2016.06.006
Sperduto, Paul W. ; Yang, T. Jonathan ; Beal, Kathryn ; Pan, Hubert ; Brown, Paul D. ; Bangdiwala, Ananta ; Shanley, Ryan ; Yeh, Norman ; Gaspar, Laurie E. ; Braunstein, Steve ; Sneed, Penny ; Boyle, John ; Kirkpatrick, John P. ; Mak, Kimberley S. ; Shih, Helen A. ; Engelman, Alex ; Roberge, David ; Arvold, Nils D. ; Alexander, Brian ; Awad, Mark M. ; Contessa, Joseph ; Chiang, Veronica ; Hardie, John ; Ma, Daniel ; Lou, Emil ; Sperduto, William ; Mehta, Minesh P. / The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases. In: International Journal of Radiation Oncology Biology Physics. 2016 ; Vol. 96, No. 2. pp. 406-413.
@article{ee2d3e7ac03e4f4293ae241fdb1727f1,
title = "The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases",
abstract = "Purpose Lung cancer remains the most common cause of both cancer mortality and brain metastases (BM). The purpose of this study was to assess the effect of gene alterations and tyrosine kinase inhibition (TKI) on median survival (MS) and cause of death (CoD) in patients with BM from lung adenocarcinoma (L-adeno). Methods A multi-institutional retrospective database of patients with L-adeno and newly diagnosed BM between 2006 and 2014 was created. Demographics, gene alterations, treatment, MS, and CoD were analyzed. The treatment patterns and outcomes were compared with those in prior trials. Results Of 1521 L-adeno patients, 816 (54{\%}) had known alteration status. The gene alteration rates were 29{\%}, 10{\%}, and 26{\%} for EGFR, ALK, and KRAS, respectively. The time from primary diagnosis to BM for EGFR−/+ was 10/15 months (P=.02) and for ALK−/+ was 10/20 months (P<.01), respectively. The MS for the group overall (n=1521) was 15 months. The MS from first treatment for BM for EGFR and ALK−, EGFR+, ALK+ were 14, 23 (P<.01), and 45 (P<.0001) months, respectively. The MS after BM for EGFR+ patients who did/did not receive TKI before BM was 17/30 months (P<.01), respectively, but the risk of death was not statistically different between TKI-na{\"i}ve patients who did/did not receive TKI after the diagnosis of BM (EGFR/ALK hazard ratios: 1.06 [P=.84]/1.60 [P=.45], respectively). The CoD was nonneurologic in 82{\%} of patients with known CoD. Conclusion EGFR and ALK gene alterations are associated with delayed onset of BM and longer MS relative to patients without these alterations. The CoD was overwhelmingly nonneurologic in patients with known CoD.",
author = "Sperduto, {Paul W.} and Yang, {T. Jonathan} and Kathryn Beal and Hubert Pan and Brown, {Paul D.} and Ananta Bangdiwala and Ryan Shanley and Norman Yeh and Gaspar, {Laurie E.} and Steve Braunstein and Penny Sneed and John Boyle and Kirkpatrick, {John P.} and Mak, {Kimberley S.} and Shih, {Helen A.} and Alex Engelman and David Roberge and Arvold, {Nils D.} and Brian Alexander and Awad, {Mark M.} and Joseph Contessa and Veronica Chiang and John Hardie and Daniel Ma and Emil Lou and William Sperduto and Mehta, {Minesh P.}",
year = "2016",
month = "10",
day = "1",
doi = "10.1016/j.ijrobp.2016.06.006",
language = "English (US)",
volume = "96",
pages = "406--413",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases

AU - Sperduto, Paul W.

AU - Yang, T. Jonathan

AU - Beal, Kathryn

AU - Pan, Hubert

AU - Brown, Paul D.

AU - Bangdiwala, Ananta

AU - Shanley, Ryan

AU - Yeh, Norman

AU - Gaspar, Laurie E.

AU - Braunstein, Steve

AU - Sneed, Penny

AU - Boyle, John

AU - Kirkpatrick, John P.

AU - Mak, Kimberley S.

AU - Shih, Helen A.

AU - Engelman, Alex

AU - Roberge, David

AU - Arvold, Nils D.

AU - Alexander, Brian

AU - Awad, Mark M.

AU - Contessa, Joseph

AU - Chiang, Veronica

AU - Hardie, John

AU - Ma, Daniel

AU - Lou, Emil

AU - Sperduto, William

AU - Mehta, Minesh P.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Purpose Lung cancer remains the most common cause of both cancer mortality and brain metastases (BM). The purpose of this study was to assess the effect of gene alterations and tyrosine kinase inhibition (TKI) on median survival (MS) and cause of death (CoD) in patients with BM from lung adenocarcinoma (L-adeno). Methods A multi-institutional retrospective database of patients with L-adeno and newly diagnosed BM between 2006 and 2014 was created. Demographics, gene alterations, treatment, MS, and CoD were analyzed. The treatment patterns and outcomes were compared with those in prior trials. Results Of 1521 L-adeno patients, 816 (54%) had known alteration status. The gene alteration rates were 29%, 10%, and 26% for EGFR, ALK, and KRAS, respectively. The time from primary diagnosis to BM for EGFR−/+ was 10/15 months (P=.02) and for ALK−/+ was 10/20 months (P<.01), respectively. The MS for the group overall (n=1521) was 15 months. The MS from first treatment for BM for EGFR and ALK−, EGFR+, ALK+ were 14, 23 (P<.01), and 45 (P<.0001) months, respectively. The MS after BM for EGFR+ patients who did/did not receive TKI before BM was 17/30 months (P<.01), respectively, but the risk of death was not statistically different between TKI-naïve patients who did/did not receive TKI after the diagnosis of BM (EGFR/ALK hazard ratios: 1.06 [P=.84]/1.60 [P=.45], respectively). The CoD was nonneurologic in 82% of patients with known CoD. Conclusion EGFR and ALK gene alterations are associated with delayed onset of BM and longer MS relative to patients without these alterations. The CoD was overwhelmingly nonneurologic in patients with known CoD.

AB - Purpose Lung cancer remains the most common cause of both cancer mortality and brain metastases (BM). The purpose of this study was to assess the effect of gene alterations and tyrosine kinase inhibition (TKI) on median survival (MS) and cause of death (CoD) in patients with BM from lung adenocarcinoma (L-adeno). Methods A multi-institutional retrospective database of patients with L-adeno and newly diagnosed BM between 2006 and 2014 was created. Demographics, gene alterations, treatment, MS, and CoD were analyzed. The treatment patterns and outcomes were compared with those in prior trials. Results Of 1521 L-adeno patients, 816 (54%) had known alteration status. The gene alteration rates were 29%, 10%, and 26% for EGFR, ALK, and KRAS, respectively. The time from primary diagnosis to BM for EGFR−/+ was 10/15 months (P=.02) and for ALK−/+ was 10/20 months (P<.01), respectively. The MS for the group overall (n=1521) was 15 months. The MS from first treatment for BM for EGFR and ALK−, EGFR+, ALK+ were 14, 23 (P<.01), and 45 (P<.0001) months, respectively. The MS after BM for EGFR+ patients who did/did not receive TKI before BM was 17/30 months (P<.01), respectively, but the risk of death was not statistically different between TKI-naïve patients who did/did not receive TKI after the diagnosis of BM (EGFR/ALK hazard ratios: 1.06 [P=.84]/1.60 [P=.45], respectively). The CoD was nonneurologic in 82% of patients with known CoD. Conclusion EGFR and ALK gene alterations are associated with delayed onset of BM and longer MS relative to patients without these alterations. The CoD was overwhelmingly nonneurologic in patients with known CoD.

UR - http://www.scopus.com/inward/record.url?scp=84994491657&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994491657&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2016.06.006

DO - 10.1016/j.ijrobp.2016.06.006

M3 - Article

C2 - 27598807

AN - SCOPUS:84994491657

VL - 96

SP - 406

EP - 413

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 2

ER -