Ipilimumab and radiation therapy for melanoma brain metastases
TLDR
Ipilimumab is associated with a significantly reduced risk of death in patients with melanoma brain metastases who underwent radiotherapy, and this finding supports the need for multimodality therapy to optimize patient outcomes.Abstract:
Ipilimumab, an antibody that enhances T-cell activation, may augment immunogenicity of tumor cells that are injured by radiation therapy. We hypothesized that patients with melanoma brain metastasis treated with both ipilimumab and radiotherapy would have improved overall survival, and that the sequence of treatments may affect disease control in the brain. We analyzed the clinical and radiographic records of melanoma patients with brain metastases who were treated with whole brain radiation therapy or stereotactic radiosurgery between 2005 and 2012. The hazard ratios for survival were estimated to assess outcomes as a function of ipilimumab use and radiation type. Seventy patients were identified, 33 of whom received ipilimumab and 37 who did not. The patients who received ipilimumab had a censored median survival of 18.3 months (95% confidence interval 8.1–25.5), compared with 5.3 months (95% confidence interval 4.0–7.6) for patients who did not receive ipilimumab. Ipilimumab and stereotactic radiosurgery were each significant predictors of improved overall survival (hazard ratio = 0.43 and 0.45, with P = 0.005 and 0.008, respectively). Four of 10 evaluable patients (40.0%) who received ipilimumab prior to radiotherapy demonstrated a partial response to radiotherapy, compared with two of 22 evaluable patients (9.1%) who did not receive ipilimumab. Ipilimumab is associated with a significantly reduced risk of death in patients with melanoma brain metastases who underwent radiotherapy, and this finding supports the need for multimodality therapy to optimize patient outcomes. Prospective studies are needed and are underway.read more
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Journal ArticleDOI
Combination therapy with anti-PD-1, anti-TIM-3, and focal radiation results in regression of murine gliomas
Jennifer E. Kim,Mira A. Patel,Antonella Mangraviti,Eileen S. Kim,Debebe Theodros,Esteban Velarde,Ann Liu,Eric W. Sankey,Ada Tam,Haiying Xu,Dimitrios Mathios,Christopher M. Jackson,Sarah Harris-Bookman,Tomas Garzon-Muvdi,Mary Sheu,Allison Martin,Betty Tyler,Phuoc T. Tran,Xiaobu Ye,Alessandro Olivi,Janis M. Taube,Peter C. Burger,Charles G. Drake,Henry Brem,Drew M. Pardoll,Michael Lim +25 more
TL;DR: This is the first preclinical investigation on the effects of dual PD-1 and TIM-3 blockade with radiation and provides preclinical evidence for a novel treatment combination that can potentially result in long-term glioma survival and constitutes a novel immunotherapeutic strategy for the treatment of glioblastoma multiforme.
Journal ArticleDOI
Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: individual patient data meta-analysis.
Arjun Sahgal,Hidefumi Aoyama,Martin Kocher,Binod Neupane,Sandra Collette,Masao Tago,Prakesh Shaw,Joseph Beyene,Eric L. Chang +8 more
TL;DR: For patients ≤50 years of age, SRS alone favored survival, in addition, the initial omission of WBRT did not impact distant brain relapse rates, and S RS alone may be the preferred treatment for this age group.
Phase 3 Trials of Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for 1 to 4 Brain Metastases: Individual Patient
Arjun Sahgal,Hidefumi Aoyama,Martin Kocher,Binod Neupane,Sandra Collette,Masao Tago,Prakesh S. Shah,Joseph Beyene,Eric L. Chang +8 more
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Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach?
TL;DR: The preclinical and clinical evidence supporting activation of the immune system following SABR is explored and general guiding principles for the development of future clinical trials to investigate the efficacy of ISABR are provided in the hope of generating further interest in these exciting developments.
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Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma.
Linda Chen,Jacqueline Douglass,Lawrence Kleinberg,Xiaobu Ye,Ariel E. Marciscano,Patrick M. Forde,Julie R. Brahmer,Evan J. Lipson,William H. Sharfman,Hans J. Hammers,Jarushka Naidoo,Chetan Bettegowda,Michael Lim,Kristin J. Redmond +13 more
TL;DR: Delivering SRS-SRT with concurrent ICI may be associated with a decreased incidence of new BMs and favorable survival outcomes without increased rates of adverse events.
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TL;DR: Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dACarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma.
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Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response Criteria
Jedd D. Wolchok,Axel Hoos,Steven J. O'Day,Jeffrey S. Weber,Omid Hamid,Céleste Lebbé,Michele Maio,Michael Binder,Oliver Bohnsack,Geoffrey M. Nichol,R. Humphrey,F. Stephen Hodi +11 more
TL;DR: Systematic criteria, designated immune-related response criteria, were defined in an attempt to capture additional response patterns observed with immune therapy in advanced melanoma beyond those described by Response Evaluation Criteria in Solid Tumors or WHO criteria.
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