Stereotactic radiosurgery of early melanoma brain metastases after initiation of anti-CTL-4 treatment is associated with improved intracranial control

Yi An, Wen Jiang, Y S Betty Kim, Jack M. Qian, Chad Tang, Penny Fang, Jennifer Logan, Neil M. D'Souza, Lauren E. Haydu, Xin A. Wang, Kenneth R. Hess, Harriet Kluger, Isabella C. Glitza, Anita Mahajan, James W. Welsh, Steven H. Lin, James B. Yu, Michael A. Davies, Patrick Hwu, Erik P. Sulman & 3 others Paul D. Brown, Veronica L.S. Chiang, Jing Li

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Numerous studies suggest that radiation can boost antitumor immune response by stimulating release of tumor-specific antigens. However, the optimal timing between radiotherapy and immune checkpoint blockade to achieve potentially synergistic benefits is unclear. Material and methods: Multi-institutional retrospective analysis was conducted of ninety-nine metastatic melanoma patients from 2007 to 2014 treated with ipilimumab who later received stereotactic radiosurgery (SRS) for new brain metastases that developed after starting immunotherapy. All patients had complete blood count acquired before SRS. Primary outcomes were intracranial disease control and overall survival (OS). Results: The median follow-up time was 15.5. months. In the MD Anderson cohort, patients who received SRS after 5.5. months (n = 20) of their last dose of ipilimumab had significantly worse intracranial control than patients who received SRS within 5.5. months (n = 51) (median 3.63 vs. 8.09. months; hazard ratio [HR] 2.07, 95% confidence interval [CI] 1.03-4.16, p = 0.041). OS was not different between the two arms. The improvement in intracranial control was confirmed in an independent validation cohort of 28 patients treated at Yale-New Haven Hospital. Circulating absolute lymphocyte count before SRS predicted for treatment response as those with baseline counts >1000/μL had reduced risk of intracranial recurrence compared with those with ≤1000/μL (HR 0.46, 95% CI 0.0.23-0.94, p = 0.03). Conclusions: In this multi-institutional study, patients who received SRS for new brain metastases within 5.5. months after ipilimumab therapy had better intracranial disease control than those who received SRS later. Moreover, higher circulating lymphocyte count was associated with improved intracranial disease control.

Original languageEnglish (US)
JournalRadiotherapy and Oncology
DOIs
StateAccepted/In press - 2017

Fingerprint

Radiosurgery
Melanoma
Neoplasm Metastasis
Brain
Lymphocyte Count
Therapeutics
Confidence Intervals
Survival
Blood Cell Count
Neoplasm Antigens
Immunotherapy
Radiotherapy
Radiation
Recurrence
ipilimumab

Keywords

  • Brain metastases
  • Immunotherapy
  • Melanoma
  • Radiosurgery

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Stereotactic radiosurgery of early melanoma brain metastases after initiation of anti-CTL-4 treatment is associated with improved intracranial control. / An, Yi; Jiang, Wen; Kim, Y S Betty; Qian, Jack M.; Tang, Chad; Fang, Penny; Logan, Jennifer; D'Souza, Neil M.; Haydu, Lauren E.; Wang, Xin A.; Hess, Kenneth R.; Kluger, Harriet; Glitza, Isabella C.; Mahajan, Anita; Welsh, James W.; Lin, Steven H.; Yu, James B.; Davies, Michael A.; Hwu, Patrick; Sulman, Erik P.; Brown, Paul D.; Chiang, Veronica L.S.; Li, Jing.

In: Radiotherapy and Oncology, 2017.

Research output: Contribution to journalArticle

An, Y, Jiang, W, Kim, YSB, Qian, JM, Tang, C, Fang, P, Logan, J, D'Souza, NM, Haydu, LE, Wang, XA, Hess, KR, Kluger, H, Glitza, IC, Mahajan, A, Welsh, JW, Lin, SH, Yu, JB, Davies, MA, Hwu, P, Sulman, EP, Brown, PD, Chiang, VLS & Li, J 2017, 'Stereotactic radiosurgery of early melanoma brain metastases after initiation of anti-CTL-4 treatment is associated with improved intracranial control', Radiotherapy and Oncology. https://doi.org/10.1016/j.radonc.2017.08.009
An, Yi ; Jiang, Wen ; Kim, Y S Betty ; Qian, Jack M. ; Tang, Chad ; Fang, Penny ; Logan, Jennifer ; D'Souza, Neil M. ; Haydu, Lauren E. ; Wang, Xin A. ; Hess, Kenneth R. ; Kluger, Harriet ; Glitza, Isabella C. ; Mahajan, Anita ; Welsh, James W. ; Lin, Steven H. ; Yu, James B. ; Davies, Michael A. ; Hwu, Patrick ; Sulman, Erik P. ; Brown, Paul D. ; Chiang, Veronica L.S. ; Li, Jing. / Stereotactic radiosurgery of early melanoma brain metastases after initiation of anti-CTL-4 treatment is associated with improved intracranial control. In: Radiotherapy and Oncology. 2017.
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title = "Stereotactic radiosurgery of early melanoma brain metastases after initiation of anti-CTL-4 treatment is associated with improved intracranial control",
abstract = "Background: Numerous studies suggest that radiation can boost antitumor immune response by stimulating release of tumor-specific antigens. However, the optimal timing between radiotherapy and immune checkpoint blockade to achieve potentially synergistic benefits is unclear. Material and methods: Multi-institutional retrospective analysis was conducted of ninety-nine metastatic melanoma patients from 2007 to 2014 treated with ipilimumab who later received stereotactic radiosurgery (SRS) for new brain metastases that developed after starting immunotherapy. All patients had complete blood count acquired before SRS. Primary outcomes were intracranial disease control and overall survival (OS). Results: The median follow-up time was 15.5. months. In the MD Anderson cohort, patients who received SRS after 5.5. months (n = 20) of their last dose of ipilimumab had significantly worse intracranial control than patients who received SRS within 5.5. months (n = 51) (median 3.63 vs. 8.09. months; hazard ratio [HR] 2.07, 95{\%} confidence interval [CI] 1.03-4.16, p = 0.041). OS was not different between the two arms. The improvement in intracranial control was confirmed in an independent validation cohort of 28 patients treated at Yale-New Haven Hospital. Circulating absolute lymphocyte count before SRS predicted for treatment response as those with baseline counts >1000/μL had reduced risk of intracranial recurrence compared with those with ≤1000/μL (HR 0.46, 95{\%} CI 0.0.23-0.94, p = 0.03). Conclusions: In this multi-institutional study, patients who received SRS for new brain metastases within 5.5. months after ipilimumab therapy had better intracranial disease control than those who received SRS later. Moreover, higher circulating lymphocyte count was associated with improved intracranial disease control.",
keywords = "Brain metastases, Immunotherapy, Melanoma, Radiosurgery",
author = "Yi An and Wen Jiang and Kim, {Y S Betty} and Qian, {Jack M.} and Chad Tang and Penny Fang and Jennifer Logan and D'Souza, {Neil M.} and Haydu, {Lauren E.} and Wang, {Xin A.} and Hess, {Kenneth R.} and Harriet Kluger and Glitza, {Isabella C.} and Anita Mahajan and Welsh, {James W.} and Lin, {Steven H.} and Yu, {James B.} and Davies, {Michael A.} and Patrick Hwu and Sulman, {Erik P.} and Brown, {Paul D.} and Chiang, {Veronica L.S.} and Jing Li",
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TY - JOUR

T1 - Stereotactic radiosurgery of early melanoma brain metastases after initiation of anti-CTL-4 treatment is associated with improved intracranial control

AU - An, Yi

AU - Jiang, Wen

AU - Kim, Y S Betty

AU - Qian, Jack M.

AU - Tang, Chad

AU - Fang, Penny

AU - Logan, Jennifer

AU - D'Souza, Neil M.

AU - Haydu, Lauren E.

AU - Wang, Xin A.

AU - Hess, Kenneth R.

AU - Kluger, Harriet

AU - Glitza, Isabella C.

AU - Mahajan, Anita

AU - Welsh, James W.

AU - Lin, Steven H.

AU - Yu, James B.

AU - Davies, Michael A.

AU - Hwu, Patrick

AU - Sulman, Erik P.

AU - Brown, Paul D.

AU - Chiang, Veronica L.S.

AU - Li, Jing

PY - 2017

Y1 - 2017

N2 - Background: Numerous studies suggest that radiation can boost antitumor immune response by stimulating release of tumor-specific antigens. However, the optimal timing between radiotherapy and immune checkpoint blockade to achieve potentially synergistic benefits is unclear. Material and methods: Multi-institutional retrospective analysis was conducted of ninety-nine metastatic melanoma patients from 2007 to 2014 treated with ipilimumab who later received stereotactic radiosurgery (SRS) for new brain metastases that developed after starting immunotherapy. All patients had complete blood count acquired before SRS. Primary outcomes were intracranial disease control and overall survival (OS). Results: The median follow-up time was 15.5. months. In the MD Anderson cohort, patients who received SRS after 5.5. months (n = 20) of their last dose of ipilimumab had significantly worse intracranial control than patients who received SRS within 5.5. months (n = 51) (median 3.63 vs. 8.09. months; hazard ratio [HR] 2.07, 95% confidence interval [CI] 1.03-4.16, p = 0.041). OS was not different between the two arms. The improvement in intracranial control was confirmed in an independent validation cohort of 28 patients treated at Yale-New Haven Hospital. Circulating absolute lymphocyte count before SRS predicted for treatment response as those with baseline counts >1000/μL had reduced risk of intracranial recurrence compared with those with ≤1000/μL (HR 0.46, 95% CI 0.0.23-0.94, p = 0.03). Conclusions: In this multi-institutional study, patients who received SRS for new brain metastases within 5.5. months after ipilimumab therapy had better intracranial disease control than those who received SRS later. Moreover, higher circulating lymphocyte count was associated with improved intracranial disease control.

AB - Background: Numerous studies suggest that radiation can boost antitumor immune response by stimulating release of tumor-specific antigens. However, the optimal timing between radiotherapy and immune checkpoint blockade to achieve potentially synergistic benefits is unclear. Material and methods: Multi-institutional retrospective analysis was conducted of ninety-nine metastatic melanoma patients from 2007 to 2014 treated with ipilimumab who later received stereotactic radiosurgery (SRS) for new brain metastases that developed after starting immunotherapy. All patients had complete blood count acquired before SRS. Primary outcomes were intracranial disease control and overall survival (OS). Results: The median follow-up time was 15.5. months. In the MD Anderson cohort, patients who received SRS after 5.5. months (n = 20) of their last dose of ipilimumab had significantly worse intracranial control than patients who received SRS within 5.5. months (n = 51) (median 3.63 vs. 8.09. months; hazard ratio [HR] 2.07, 95% confidence interval [CI] 1.03-4.16, p = 0.041). OS was not different between the two arms. The improvement in intracranial control was confirmed in an independent validation cohort of 28 patients treated at Yale-New Haven Hospital. Circulating absolute lymphocyte count before SRS predicted for treatment response as those with baseline counts >1000/μL had reduced risk of intracranial recurrence compared with those with ≤1000/μL (HR 0.46, 95% CI 0.0.23-0.94, p = 0.03). Conclusions: In this multi-institutional study, patients who received SRS for new brain metastases within 5.5. months after ipilimumab therapy had better intracranial disease control than those who received SRS later. Moreover, higher circulating lymphocyte count was associated with improved intracranial disease control.

KW - Brain metastases

KW - Immunotherapy

KW - Melanoma

KW - Radiosurgery

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U2 - 10.1016/j.radonc.2017.08.009

DO - 10.1016/j.radonc.2017.08.009

M3 - Article

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

SN - 0167-8140

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