Extended survival and prognostic factors for patients with ALK-rearranged non-small-cell lung cancer and brain metastasis

Kimberly L. Johung, Norman Yeh, Neil B. Desai, Terence M. Williams, Tim Lautenschlaeger, Nils D. Arvold, Matthew S. Ning, Albert Attia, Christine M. Lovly, Sarah Goldberg, Kathryn Beal, James B. Yu, Brian D. Kavanagh, Veronica L. Chiang, D. Ross Camidge, Joseph N. Contessa

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

Purpose. We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and brain metastasis. Patients and Methods A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling. Results. Median OS after development of brain metastases was 49.5 months (95% CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95% CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score ≥ 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, < .001, and < .001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P=.633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33%, 59%, 76%, and 100%, respectively (P<.001). Conclusion. Patientswith brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line SRS, close CNS observation, and treatment of emergent CNS disease.

Original languageEnglish (US)
Pages (from-to)123-129
Number of pages7
JournalJournal of Clinical Oncology
Volume34
Issue number2
DOIs
StatePublished - Jan 10 2016

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Non-Small Cell Lung Carcinoma
Brain Neoplasms
Neoplasm Metastasis
Survival
Brain
Radiosurgery
Radiotherapy
Disease-Free Survival
Central Nervous System Diseases
Protein-Tyrosine Kinases
Therapeutics
Observation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Extended survival and prognostic factors for patients with ALK-rearranged non-small-cell lung cancer and brain metastasis. / Johung, Kimberly L.; Yeh, Norman; Desai, Neil B.; Williams, Terence M.; Lautenschlaeger, Tim; Arvold, Nils D.; Ning, Matthew S.; Attia, Albert; Lovly, Christine M.; Goldberg, Sarah; Beal, Kathryn; Yu, James B.; Kavanagh, Brian D.; Chiang, Veronica L.; Camidge, D. Ross; Contessa, Joseph N.

In: Journal of Clinical Oncology, Vol. 34, No. 2, 10.01.2016, p. 123-129.

Research output: Contribution to journalArticle

Johung, KL, Yeh, N, Desai, NB, Williams, TM, Lautenschlaeger, T, Arvold, ND, Ning, MS, Attia, A, Lovly, CM, Goldberg, S, Beal, K, Yu, JB, Kavanagh, BD, Chiang, VL, Camidge, DR & Contessa, JN 2016, 'Extended survival and prognostic factors for patients with ALK-rearranged non-small-cell lung cancer and brain metastasis', Journal of Clinical Oncology, vol. 34, no. 2, pp. 123-129. https://doi.org/10.1200/JCO.2015.62.0138
Johung, Kimberly L. ; Yeh, Norman ; Desai, Neil B. ; Williams, Terence M. ; Lautenschlaeger, Tim ; Arvold, Nils D. ; Ning, Matthew S. ; Attia, Albert ; Lovly, Christine M. ; Goldberg, Sarah ; Beal, Kathryn ; Yu, James B. ; Kavanagh, Brian D. ; Chiang, Veronica L. ; Camidge, D. Ross ; Contessa, Joseph N. / Extended survival and prognostic factors for patients with ALK-rearranged non-small-cell lung cancer and brain metastasis. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 2. pp. 123-129.
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abstract = "Purpose. We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and brain metastasis. Patients and Methods A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling. Results. Median OS after development of brain metastases was 49.5 months (95{\%} CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95{\%} CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score ≥ 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, < .001, and < .001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P=.633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33{\%}, 59{\%}, 76{\%}, and 100{\%}, respectively (P<.001). Conclusion. Patientswith brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line SRS, close CNS observation, and treatment of emergent CNS disease.",
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T1 - Extended survival and prognostic factors for patients with ALK-rearranged non-small-cell lung cancer and brain metastasis

AU - Johung, Kimberly L.

AU - Yeh, Norman

AU - Desai, Neil B.

AU - Williams, Terence M.

AU - Lautenschlaeger, Tim

AU - Arvold, Nils D.

AU - Ning, Matthew S.

AU - Attia, Albert

AU - Lovly, Christine M.

AU - Goldberg, Sarah

AU - Beal, Kathryn

AU - Yu, James B.

AU - Kavanagh, Brian D.

AU - Chiang, Veronica L.

AU - Camidge, D. Ross

AU - Contessa, Joseph N.

PY - 2016/1/10

Y1 - 2016/1/10

N2 - Purpose. We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and brain metastasis. Patients and Methods A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling. Results. Median OS after development of brain metastases was 49.5 months (95% CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95% CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score ≥ 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, < .001, and < .001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P=.633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33%, 59%, 76%, and 100%, respectively (P<.001). Conclusion. Patientswith brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line SRS, close CNS observation, and treatment of emergent CNS disease.

AB - Purpose. We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and brain metastasis. Patients and Methods A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling. Results. Median OS after development of brain metastases was 49.5 months (95% CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95% CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score ≥ 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, < .001, and < .001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P=.633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33%, 59%, 76%, and 100%, respectively (P<.001). Conclusion. Patientswith brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line SRS, close CNS observation, and treatment of emergent CNS disease.

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