Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: Safety profile and efficacy of combined treatment

Ana Ponce Kiess, Jedd D. Wolchok, Christopher A. Barker, Michael A. Postow, Viviane Tabar, Jason T. Huse, Timothy A. Chan, Yoshiya Yamada, Kathryn Beal

Research output: Contribution to journalArticle

Abstract

Purpose Ipilimumab (Ipi), a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, has been shown to improve survival in patients with metastatic melanoma. In this single-institution study, we investigated the safety and efficacy of stereotactic radiosurgery (SRS) for patients with melanoma brain metastases (BMs) who also received Ipi. Methods and Materials From 2005 to 2011, 46 patients with melanoma received Ipi and underwent single-fraction SRS for BMs. A total of 113 BMs (91% intact, 9% postoperative) were treated with a median dose of 21 Gy (range, 15-24 Gy). Ipi was given at 3 mg/kg (54%) or 10 mg/kg (46%) for a median of 4 doses (range, 1-21). Adverse events were recorded with the use of the Common Terminology Criteria for Adverse Events 3.0. Kaplan-Meier methods were used to estimate survival, and Cox regression was used to investigate associations. Results Fifteen patients received SRS during Ipi, 19 received SRS before Ipi, and 12 received SRS after Ipi. Overall survival (OS) was significantly associated with the timing of SRS/Ipi (P=.035) and melanoma-specific graded prognostic assessment (P=.013). Patients treated with SRS during or before Ipi had better OS and less regional recurrence than did those treated with SRS after Ipi (1-year OS 65% vs 56% vs 40%, P=.008; 1-year regional recurrence 69% vs 64% vs 92%, P=.003). SRS during Ipi also yielded a trend toward less local recurrence than did SRS before or after Ipi (1-year local recurrence 0% vs 13% vs 11%, P=.21). On magnetic resonance imaging, an increase in BM diameter to >150% was seen in 50% of patients treated during or before Ipi but in only 13% of patients treated after Ipi. Grade 3 to 4 toxicities were seen in 20% of patients. Conclusion Overall, the combination of Ipi and SRS appears to be well tolerated. Concurrent delivery of Ipi and SRS is associated with favorable locoregional control and possibly longer survival. It may also cause a temporary increase in tumor size, possibly because of an enhanced immunomodulatory effect.

Original languageEnglish (US)
Pages (from-to)368-375
Number of pages8
JournalInternational Journal of Radiation Oncology, Biology, Physics
Volume92
Issue number2
DOIs
StatePublished - Jun 1 2015

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Radiosurgery
metastasis
brain
Melanoma
safety
Neoplasm Metastasis
Safety
Brain
profiles
Survival
Recurrence
dosage
terminology
ipilimumab
lymphocytes
antigens
antibodies
toxicity
magnetic resonance
regression analysis

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research
  • Medicine(all)

Cite this

Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab : Safety profile and efficacy of combined treatment. / Kiess, Ana Ponce; Wolchok, Jedd D.; Barker, Christopher A.; Postow, Michael A.; Tabar, Viviane; Huse, Jason T.; Chan, Timothy A.; Yamada, Yoshiya; Beal, Kathryn.

In: International Journal of Radiation Oncology, Biology, Physics, Vol. 92, No. 2, 01.06.2015, p. 368-375.

Research output: Contribution to journalArticle

Kiess, Ana Ponce ; Wolchok, Jedd D. ; Barker, Christopher A. ; Postow, Michael A. ; Tabar, Viviane ; Huse, Jason T. ; Chan, Timothy A. ; Yamada, Yoshiya ; Beal, Kathryn. / Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab : Safety profile and efficacy of combined treatment. In: International Journal of Radiation Oncology, Biology, Physics. 2015 ; Vol. 92, No. 2. pp. 368-375.
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abstract = "Purpose Ipilimumab (Ipi), a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, has been shown to improve survival in patients with metastatic melanoma. In this single-institution study, we investigated the safety and efficacy of stereotactic radiosurgery (SRS) for patients with melanoma brain metastases (BMs) who also received Ipi. Methods and Materials From 2005 to 2011, 46 patients with melanoma received Ipi and underwent single-fraction SRS for BMs. A total of 113 BMs (91{\%} intact, 9{\%} postoperative) were treated with a median dose of 21 Gy (range, 15-24 Gy). Ipi was given at 3 mg/kg (54{\%}) or 10 mg/kg (46{\%}) for a median of 4 doses (range, 1-21). Adverse events were recorded with the use of the Common Terminology Criteria for Adverse Events 3.0. Kaplan-Meier methods were used to estimate survival, and Cox regression was used to investigate associations. Results Fifteen patients received SRS during Ipi, 19 received SRS before Ipi, and 12 received SRS after Ipi. Overall survival (OS) was significantly associated with the timing of SRS/Ipi (P=.035) and melanoma-specific graded prognostic assessment (P=.013). Patients treated with SRS during or before Ipi had better OS and less regional recurrence than did those treated with SRS after Ipi (1-year OS 65{\%} vs 56{\%} vs 40{\%}, P=.008; 1-year regional recurrence 69{\%} vs 64{\%} vs 92{\%}, P=.003). SRS during Ipi also yielded a trend toward less local recurrence than did SRS before or after Ipi (1-year local recurrence 0{\%} vs 13{\%} vs 11{\%}, P=.21). On magnetic resonance imaging, an increase in BM diameter to >150{\%} was seen in 50{\%} of patients treated during or before Ipi but in only 13{\%} of patients treated after Ipi. Grade 3 to 4 toxicities were seen in 20{\%} of patients. Conclusion Overall, the combination of Ipi and SRS appears to be well tolerated. Concurrent delivery of Ipi and SRS is associated with favorable locoregional control and possibly longer survival. It may also cause a temporary increase in tumor size, possibly because of an enhanced immunomodulatory effect.",
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T2 - Safety profile and efficacy of combined treatment

AU - Kiess, Ana Ponce

AU - Wolchok, Jedd D.

AU - Barker, Christopher A.

AU - Postow, Michael A.

AU - Tabar, Viviane

AU - Huse, Jason T.

AU - Chan, Timothy A.

AU - Yamada, Yoshiya

AU - Beal, Kathryn

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N2 - Purpose Ipilimumab (Ipi), a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, has been shown to improve survival in patients with metastatic melanoma. In this single-institution study, we investigated the safety and efficacy of stereotactic radiosurgery (SRS) for patients with melanoma brain metastases (BMs) who also received Ipi. Methods and Materials From 2005 to 2011, 46 patients with melanoma received Ipi and underwent single-fraction SRS for BMs. A total of 113 BMs (91% intact, 9% postoperative) were treated with a median dose of 21 Gy (range, 15-24 Gy). Ipi was given at 3 mg/kg (54%) or 10 mg/kg (46%) for a median of 4 doses (range, 1-21). Adverse events were recorded with the use of the Common Terminology Criteria for Adverse Events 3.0. Kaplan-Meier methods were used to estimate survival, and Cox regression was used to investigate associations. Results Fifteen patients received SRS during Ipi, 19 received SRS before Ipi, and 12 received SRS after Ipi. Overall survival (OS) was significantly associated with the timing of SRS/Ipi (P=.035) and melanoma-specific graded prognostic assessment (P=.013). Patients treated with SRS during or before Ipi had better OS and less regional recurrence than did those treated with SRS after Ipi (1-year OS 65% vs 56% vs 40%, P=.008; 1-year regional recurrence 69% vs 64% vs 92%, P=.003). SRS during Ipi also yielded a trend toward less local recurrence than did SRS before or after Ipi (1-year local recurrence 0% vs 13% vs 11%, P=.21). On magnetic resonance imaging, an increase in BM diameter to >150% was seen in 50% of patients treated during or before Ipi but in only 13% of patients treated after Ipi. Grade 3 to 4 toxicities were seen in 20% of patients. Conclusion Overall, the combination of Ipi and SRS appears to be well tolerated. Concurrent delivery of Ipi and SRS is associated with favorable locoregional control and possibly longer survival. It may also cause a temporary increase in tumor size, possibly because of an enhanced immunomodulatory effect.

AB - Purpose Ipilimumab (Ipi), a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, has been shown to improve survival in patients with metastatic melanoma. In this single-institution study, we investigated the safety and efficacy of stereotactic radiosurgery (SRS) for patients with melanoma brain metastases (BMs) who also received Ipi. Methods and Materials From 2005 to 2011, 46 patients with melanoma received Ipi and underwent single-fraction SRS for BMs. A total of 113 BMs (91% intact, 9% postoperative) were treated with a median dose of 21 Gy (range, 15-24 Gy). Ipi was given at 3 mg/kg (54%) or 10 mg/kg (46%) for a median of 4 doses (range, 1-21). Adverse events were recorded with the use of the Common Terminology Criteria for Adverse Events 3.0. Kaplan-Meier methods were used to estimate survival, and Cox regression was used to investigate associations. Results Fifteen patients received SRS during Ipi, 19 received SRS before Ipi, and 12 received SRS after Ipi. Overall survival (OS) was significantly associated with the timing of SRS/Ipi (P=.035) and melanoma-specific graded prognostic assessment (P=.013). Patients treated with SRS during or before Ipi had better OS and less regional recurrence than did those treated with SRS after Ipi (1-year OS 65% vs 56% vs 40%, P=.008; 1-year regional recurrence 69% vs 64% vs 92%, P=.003). SRS during Ipi also yielded a trend toward less local recurrence than did SRS before or after Ipi (1-year local recurrence 0% vs 13% vs 11%, P=.21). On magnetic resonance imaging, an increase in BM diameter to >150% was seen in 50% of patients treated during or before Ipi but in only 13% of patients treated after Ipi. Grade 3 to 4 toxicities were seen in 20% of patients. Conclusion Overall, the combination of Ipi and SRS appears to be well tolerated. Concurrent delivery of Ipi and SRS is associated with favorable locoregional control and possibly longer survival. It may also cause a temporary increase in tumor size, possibly because of an enhanced immunomodulatory effect.

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