A phase 2 study of radiosurgery and temozolomide for patients with 1 to 4 brain metastases

Fiveash, John B.; Arafat, Waleed; Naoum, George E.; Guthrie, Barton L.; Sawrie, Stephen M.; Spencer, Sharon A.; Meredith, Ruby F.; Markert, James M.; Conry, Robert M.; Nabors, Burt

doi:10.1016/j.adro.2016.03.004

Cited by 4 publications

(2 citation statements)

References 17 publications

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“…In addition, temozolomide is metabolised to dacarbazine, one of the chemotherapeutics used in melanoma, and demonstrates selective depletion of regulatory T cells in vitro, thus offering, in theory, a triple-pronged attack. Results to date are modest however [73]. Many systemic agents are being explored but perhaps the most exciting recent report pertains to talimogene laherparepvec (T-vec), the first FDA approved oncolytic viral therapy.…”

Section: Introductionmentioning

confidence: 99%

Radiotherapy for Melanoma: More than DNA Damage

Rogers

Puric

Eberle

et al. 2019

Dermatology Research and Practice

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Despite its reputation as a radioresistant tumour, there is evidence to support a role for radiotherapy in patients with melanoma and we summarise current clinical practice. Melanoma is a highly immunogenic tumour and in this era of immunotherapy, there is renewed interest in the potential of irradiation, not only as an adjuvant and palliative treatment, but also as an immune stimulant. It has long been known that radiation causes not only DNA strand breaks, apoptosis, and necrosis, but also immunogenic modulation and cell death through the induction of dendritic cells, cell adhesion molecules, death receptors, and tumour-associated antigens, effectively transforming the tumour into an individualised vaccine. This immune response can be enhanced by the application of clinical hyperthermia as evidenced by randomised trial data in patients with melanoma. The large fraction sizes used in cranial radiosurgery and stereotactic body radiotherapy are more immunogenic than conventional fractionation, which provides additional radiobiological justification for these techniques in this disease entity. Given the immune priming effect of radiotherapy, there is a strong but complex biological rationale and an increasing body of evidence for synergy in combination with immune checkpoint inhibitors, which are now first-line therapy in patients with recurrent or metastatic melanoma. There is great potential to increase local control and abscopal effects by combining radiotherapy with both immunotherapy and hyperthermia, and a combination of all three modalities is suggested as the next important trial in this refractory disease.

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Section: Introductionmentioning

confidence: 99%

Radiotherapy for Melanoma: More than DNA Damage

Rogers

Puric

Eberle

et al. 2019

Dermatology Research and Practice

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“…Patients with histopathologic subtype, glioblastoma multiform (GBM) have the worst prognosis; despite aggressive surgery, radiation, and chemotherapy [ 1 , 2 ]. Radiation remains an integral part of the conventional treatment of brain malignancies [ 3 , 4 ]. However, many gliomas are resistant to radiotherapy [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Survivin a radiogenetic promoter for glioblastoma viral gene therapy independently from CArG motifs

Naoum¹,

Zhu

Buchsbaum

et al. 2017

Clinical & Translational Med

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Background Radiogenetic therapy is a novel approach in the treatment of cancer, which employs genetic modification to alter the sensitivity of tumor cells to the effect of applied radiation. Aim To select a potent radiation inducible promoter in the context of brain tumors and to investigate if CArG radio responsive motifs or other elements in the promoter nucleotide sequences can correlate to its response to radiation. Methods To select initial candidates for promoter inducible elements, the levels of mRNA expression of six different promoters were assessed using Quantitative RTPCR in D54 MG cells before and after radiation exposure. Recombinant Ad/reporter genes driven by five different promoters; CMV, VEGF, FLT-1, DR5 and survivin were constructed. Glioma cell lines were infected with different multiplicity of infection of the (promoter) Ad or CMV Ad. Cells were then exposed to a range of radiation (0–12 Gy) at single fraction. Fluorescent microscopy, Luc assay and X-gal staining was used to detect the level of expression of related genes. Different glioma cell lines and normal astrocytes were infected with Ad survivin and exposed to radiation. The promoters were analyzed for presence of CArG radio-responsive motifs and CCAAT box consensus using NCBI blast bioinformatics software. Results Radiotherapy increases the expression of gene expression by 1.25–2.5 fold in different promoters other than survivin after 2 h of radiation. RNA analysis was done and has shown an increase in copy number of tenfold for survivin. Most importantly cells treated with RT and Ad Luc driven by survivin promoter showed a fivefold increase in expression after 2 Gy of radiation in comparison to non-irradiated cells. Presence or absence of CArG motifs did not correlate with promoter response to radiation. Survivin with the best response to radiation had the lowest number of CCAAT box. Conclusion Survivin is a selective potent radiation inducible promoter for glioblastoma viral gene therapy and this response to radiation could be independent of CArG motifs.

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