Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT)

Anthony C. Wong, Sydeaka P. Watson, Sean P. Pitroda, Christina H. Son, Lauren C. Das, Melinda E. Stack, Abhineet Uppal, Go Oshima, Nikolai N. Khodarev, Joseph K. Salama, Ralph R. Weichselbaum, Steven J. Chmura

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

BACKGROUND: The selection of patients for oligometastasis-directed ablative therapy remains a challenge. The authors report on clinical and molecular predictors of survival from a stereotactic body radiotherapy (SBRT) dose-escalation trial for oligometastases. METHODS: Patients who had from 1 to 5 metastases, a life expectancy of >3 months, and a Karnofsky performance status of >60 received escalating SBRT doses to all known cancer sites. Time to progression, progression-free survival, and overall survival (OS) were calculated at the completion of SBRT, and clinical predictors of OS were modeled. Primary tumor microRNA expression was analyzed to identify molecular predictors of OS. RESULTS: Sixty-one evaluable patients were enrolled from 2004 to 2009. The median follow-up was 2.3 years for all patients (range, 0.2-9.3 years) and 6.8 years for survivors (range, 2.0-9.3 years). The median, 2-year, and 5-year estimated OS were 2.4 years, 57%, and 32%, respectively. The rate of progression after SBRT was associated with an increased risk of death (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.24-1.82). The time from initial cancer diagnosis to metastasis (HR, 0.98; 95% CI, 0.98-0.99), the time from metastasis to SBRT (HR, 0.98; 95% CI, 0.98-0.99), and breast cancer histology (HR, 0.12; 95% CI, 0.07-0.37) were significant predictors of OS. In an exploratory analysis, a candidate classifier using expression levels of 3 microRNAs (miR-23b, miR-449a, and miR-449b) predicted survival among 17 patients who had primary tumor microRNA expression data available. CONCLUSIONS: A subset of oligometastatic patients achieves long-term survival after metastasis-directed SBRT. Clinical features and primary tumor microRNA expression profiling, if validated in an independent dataset, may help select oligometastatic patients most likely to benefit from metastasis-directed therapy. Cancer 2016;122:2242–50.

Original languageEnglish
Pages (from-to)2242-2250
Number of pages9
JournalCancer
Volume122
Issue number14
DOIs
Publication statusPublished - 2016 Jul 15
Externally publishedYes

Fingerprint

Radiosurgery
Biomarkers
Survival
MicroRNAs
Neoplasm Metastasis
Confidence Intervals
Neoplasms
Karnofsky Performance Status
Life Expectancy
Patient Selection
Disease-Free Survival
Survivors
Histology
Breast Neoplasms
Therapeutics

Keywords

  • biomarker
  • classifier
  • microRNA
  • oligometastases
  • stereotactic body radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wong, A. C., Watson, S. P., Pitroda, S. P., Son, C. H., Das, L. C., Stack, M. E., ... Chmura, S. J. (2016). Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT). Cancer, 122(14), 2242-2250. https://doi.org/10.1002/cncr.30058

Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT). / Wong, Anthony C.; Watson, Sydeaka P.; Pitroda, Sean P.; Son, Christina H.; Das, Lauren C.; Stack, Melinda E.; Uppal, Abhineet; Oshima, Go; Khodarev, Nikolai N.; Salama, Joseph K.; Weichselbaum, Ralph R.; Chmura, Steven J.

In: Cancer, Vol. 122, No. 14, 15.07.2016, p. 2242-2250.

Research output: Contribution to journalArticle

Wong, AC, Watson, SP, Pitroda, SP, Son, CH, Das, LC, Stack, ME, Uppal, A, Oshima, G, Khodarev, NN, Salama, JK, Weichselbaum, RR & Chmura, SJ 2016, 'Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT)', Cancer, vol. 122, no. 14, pp. 2242-2250. https://doi.org/10.1002/cncr.30058
Wong, Anthony C. ; Watson, Sydeaka P. ; Pitroda, Sean P. ; Son, Christina H. ; Das, Lauren C. ; Stack, Melinda E. ; Uppal, Abhineet ; Oshima, Go ; Khodarev, Nikolai N. ; Salama, Joseph K. ; Weichselbaum, Ralph R. ; Chmura, Steven J. / Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT). In: Cancer. 2016 ; Vol. 122, No. 14. pp. 2242-2250.
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AU - Das, Lauren C.

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AU - Uppal, Abhineet

AU - Oshima, Go

AU - Khodarev, Nikolai N.

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N2 - BACKGROUND: The selection of patients for oligometastasis-directed ablative therapy remains a challenge. The authors report on clinical and molecular predictors of survival from a stereotactic body radiotherapy (SBRT) dose-escalation trial for oligometastases. METHODS: Patients who had from 1 to 5 metastases, a life expectancy of >3 months, and a Karnofsky performance status of >60 received escalating SBRT doses to all known cancer sites. Time to progression, progression-free survival, and overall survival (OS) were calculated at the completion of SBRT, and clinical predictors of OS were modeled. Primary tumor microRNA expression was analyzed to identify molecular predictors of OS. RESULTS: Sixty-one evaluable patients were enrolled from 2004 to 2009. The median follow-up was 2.3 years for all patients (range, 0.2-9.3 years) and 6.8 years for survivors (range, 2.0-9.3 years). The median, 2-year, and 5-year estimated OS were 2.4 years, 57%, and 32%, respectively. The rate of progression after SBRT was associated with an increased risk of death (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.24-1.82). The time from initial cancer diagnosis to metastasis (HR, 0.98; 95% CI, 0.98-0.99), the time from metastasis to SBRT (HR, 0.98; 95% CI, 0.98-0.99), and breast cancer histology (HR, 0.12; 95% CI, 0.07-0.37) were significant predictors of OS. In an exploratory analysis, a candidate classifier using expression levels of 3 microRNAs (miR-23b, miR-449a, and miR-449b) predicted survival among 17 patients who had primary tumor microRNA expression data available. CONCLUSIONS: A subset of oligometastatic patients achieves long-term survival after metastasis-directed SBRT. Clinical features and primary tumor microRNA expression profiling, if validated in an independent dataset, may help select oligometastatic patients most likely to benefit from metastasis-directed therapy. Cancer 2016;122:2242–50.

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