The Impact of Radiation-induced Up-regulations of IFN-γ on Local Tumor Control of Malignant Melanoma In Vivo

2012 ◽  
Vol 84 (3) ◽  
pp. S671-S672
Author(s):  
H. Ishikawa ◽  
Y. Yoshida ◽  
Y. Mutoh ◽  
S.K. Metcalfe ◽  
M. Zhang ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Local Tumor Control ◽  
Tumor Control ◽  
Local Tumor ◽  
Radiation Induced ◽  
Ifn Γ ◽  
The Impact

scholarly journals MHC Class I-Restricted TCR-Transgenic CD4+ T Cells Against STEAP1 Mediate Local Tumor Control of Ewing Sarcoma In Vivo

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1581 ◽  
Author(s):  
Sebastian J. Schober ◽  
Melanie Thiede ◽  
Hendrik Gassmann ◽  
Carolin Prexler ◽  
Busheng Xue ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class I ◽  
Cd8 T Cells ◽  
Ewing Sarcoma ◽  
Local Tumor Control ◽  
Class I ◽  
Tumor Control ◽  
Local Tumor

In this study we report the functional comparison of T cell receptor (TCR)-engineered major histocompatibility complex (MHC) class I-restricted CD4+ versus CD8+ T cells targeting a peptide from six transmembrane epithelial antigen of the prostate 1 (STEAP1) in the context of HLA-A*02:01. STEAP1 is a tumor-associated antigen, which is overexpressed in many cancers, including Ewing sarcoma (EwS). Based on previous observations, we postulated strong antitumor potential of tumor-redirected CD4+ T cells transduced with an HLA class I-restricted TCR against a STEAP1-derived peptide. We compared CD4+ T cell populations to their CD8+ counterparts in vitro using impedance-based xCELLigence and cytokine/granzyme release assays. We further compared antitumor activity of STEAP130-TCR transgenic (tg) CD4+ versus CD8+ T cells in tumor-bearing xenografted Rag2−/−γc−/− mice. TCR tgCD4+ T cells showed increased cytotoxic features over time with similar functional avidity compared to tgCD8+ cells after 5–6 weeks of culture. In vivo, local tumor control was equal. Assessing metastatic organotropism of intraveniously (i.v.) injected tumors, only tgCD8+ cells were associated with reduced metastases. In this analysis, EwS-redirected tgCD4+ T cells contribute to local tumor control, but fail to control metastatic outgrowth in a model of xenografted EwS.

BRAF V600E mutation and BRAF kinase inhibitors in conjunction with stereotactic radiosurgery for intracranial melanoma metastases

2017 ◽  
Vol 126 (3) ◽  
pp. 726-734 ◽  
Author(s):  
Zhiyuan Xu ◽  
Cheng-Chia Lee ◽  
Arjun Ramesh ◽  
Adam C. Mueller ◽  
David Schlesinger ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Local Tumor Control ◽  
Braf V600e ◽  
Tumor Control ◽  
Wild Type ◽  
Local Tumor ◽  
Mutation Status ◽  
Group A ◽  
Group B ◽  
The Impact

OBJECTIVE Recent advancements in molecular biology have identified the BRAF mutation as a common mutation in melanoma. The wide use of BRAF kinase inhibitor (BRAFi) in patients with metastatic melanoma has been established. The objective of this study was to examine the impact of BRAF mutation status and use of BRAFi in conjunction with stereotactic radiosurgery (SRS). METHODS This was a single-center retrospective study. Patient's charts and electronic records were reviewed for date of diagnosis of primary malignancy, BRAF mutation status, chemotherapies used, date of the diagnosis of CNS metastases, date of SRS, survival, local tumor control after SRS, and adverse events. Patients were divided into 3 groups: Group A, those with mutant BRAF without BRAFi treatment (13 patients); Group B, those with mutant BRAF with BRAFi treatment (17 patients); and Group C, those with wild-type BRAF (35 patients). Within a cohort of 65 patients with the known BRAF mutation status and treated with SRS between 2010 and 2014, 436 individual brain metastases (BMs) were identified. Kaplan-Meier methodology was then used to compare survival based on each binary parameter. RESULTS Median survival times after the diagnosis of melanoma BM and after SRS were favorable in patients with a BRAF mutation and treated with SRS in conjunction with BRAFi (Group B) compared with the patients with wild-type BRAF (Group C, 23 vs 8 months and 13 vs 5 months, respectively; p < 0.01, log-rank test). SRS provided a local tumor control rate of 89.4% in the entire cohort of patients. Furthermore, the local control rate was improved in the patients treated with SRS in conjunction with BRAFi (Group B) compared with patients with wild-type (Group C) or with BRAF mutation but no BRAFi (Group A) as an adjunct treatment for BMs. CONCLUSIONS BRAF mutation status appears to play an important role as a potent prognostic factor in patients harboring melanoma BM. BRAFi in conjunction with SRS may benefit this group of patients in terms of BM survival and SRS with an acceptable safety profile.

Gamma Knife surgery combined with resection for treatment of a single brain metastasis: preliminary results

2010 ◽  
Vol 113 (Special_Supplement) ◽  
pp. 90-96 ◽  
Author(s):  
M. Yashar S. Kalani ◽  
Aristotelis S. Filippidis ◽  
Maziyar A. Kalani ◽  
Nader Sanai ◽  
David Brachman ◽  
...  
Keyword(s):  
Survival Data ◽  
Initial Treatment ◽  
Median Survival Time ◽  
Local Tumor Control ◽  
Survival Duration ◽  
Tumor Control ◽  
Local Tumor ◽  
Systemic Control ◽  
Cranial Metastasis

Object Resection and whole-brain radiation therapy (WBRT) have classically been the standard treatment for a single metastasis to the brain. The objective of this study was to evaluate the use of Gamma Knife surgery (GKS) as an alternative to WBRT in patients who had undergone resection and to evaluate patient survival and local tumor control. Methods The authors retrospectively reviewed the charts of 150 patients treated with a combination of stereotactic radiosurgery and resection of a cranial metastasis at their institution between April 1997 and September 2009. Patients who had multiple lesions or underwent both WBRT and GKS were excluded, as were patients for whom survival data beyond the initial treatment were not available. Clinical and imaging follow-up was assessed using notes from clinic visits and MR imaging studies when available. Follow-up data beyond the initial treatment and survival data were available for 68 patients. Results The study included 37 women (54.4%) and 31 men (45.6%) (mean age 60 years, range 28–89 years). In 45 patients (66.2%) there was systemic control of the primary tumor when the cranial metastasis was identified. The median duration between resection and radiosurgery was 15.5 days. The median volume of the treated cavity was 10.35 cm3 (range 0.9–45.4 cm3), and the median dose to the cavity margin was 15 Gy (range 14–30 Gy), delivered to the 50% isodose line (range 50%–76% isodose line). The patients' median preradiosurgery Karnofsky Performance Scale (KPS) score was 90 (range 40–100). During the follow-up period we identified 27 patients (39.7%) with recurrent tumor located either local or distant to the site of treatment. The median time from primary treatment of metastasis to recurrence was 10.6 months. The patients' median length of survival (interval between first treatment of cerebral metastasis and last follow-up) was 13.2 months. For the patient who died during follow-up, the median time from diagnosis of cerebral metastasis to death was 11.5 months. The median duration of survival from diagnosis of the primary cancer to last follow-up was 30.2 months. Patients with a pretreatment KPS score ≥ 90 had a median survival time of 23.2 months, and patients with a pretreatment KPS score < 90 had a median survival time of 10 months (p < 0.008). Systemic control of disease at the time of metastasis was not predictive of increased survival duration, although it did tend to improve survival. Conclusions Although the debate about the ideal form of radiation treatment after resection continues, these findings indicate that GKS combined with surgery offers comparable survival duration and local tumor control to WBRT for patients with a diagnosis of a single metastasis.

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