Broad-Shouldered Survival Curves of a Human Melanoma Xenograft Implications for radiation therapy in the absence and presence of misonidazole

Rofstad, Einar K.; Brustad, Tor

doi:10.3109/02841868109130204

Cited by 16 publications

(2 citation statements)

References 27 publications

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“…Historically, adjuvant radiation for melanoma has been a controversial choice47 as early radiation studies of melanoma demonstrated wide survival curves,48 leading to the belief that melanoma is radioresistant. However, this principle has not been fully supported by clinical data.…”

Section: Radiosensitization Effect In Melanoma Cell Lines Following Bmentioning

confidence: 99%

BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy

Chowdhary¹,

Patel²,

Danish³

et al. 2016

OTT

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Melanoma is an aggressive malignancy that frequently spreads to the brain, resulting in rapid deterioration in both quality and quantity of life. Historically, treatment options for melanoma brain metastases (MBM) have predominantly consisted of surgery and radiotherapy. While these options can help provide local control, the majority of patients still develop intracranial progression. Indeed, novel therapeutic options, including molecularly targeted agents and immunotherapy, have improved outcomes and are now changing the role of radiotherapy. Up to 50% of melanomas contain an activating BRAF mutation, resulting in hyperactive cellular proliferation and survival. Drugs that target BRAF have been introduced for the treatment of metastatic melanoma and offer hope in improving disease outcomes; however, many of these trials either excluded or had a limited amount of patients with MBM. Recent studies have revealed that melanoma cell lines become more radiosensitive following BRAF inhibition, thus providing a potential synergistic mechanism when combining BRAF inhibitor (BRAFi) and radiotherapy. However, neurotoxicity concerns also exist with this combination. This article reviews the efficacy and limitations of BRAFi therapy for MBM, describes current evidence for combining BRAFis with radiation, discusses the rationale and evidence for combination modalities, and highlights emerging clinical trials specifically investigating this combination in MBM.

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Section: Radiosensitization Effect In Melanoma Cell Lines Following Bmentioning

confidence: 99%

BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy

Chowdhary¹,

Patel²,

Danish³

et al. 2016

OTT

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“…Early in vitro radiation studies of melanoma cell lines showed wide initial shoulders on survival curves leading to a widespread belief that melanomas are radioresistant and thus require high dose per fraction regimens (5–7). These early assessments however have not been supported by clinical data.…”

Section: Introductionmentioning

confidence: 99%

Melanoma cells show a heterogeneous range of sensitivity to ionizing radiation and are radiosensitized by inhibition of B-RAF with PLX-4032

Sambade

Peters

Thomas

et al. 2011

Radiotherapy and Oncology

129

109

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Purpose-To assess the relative radiosensitivities of a large collection of melanoma cell lines and to determine whether pharmacologic inhibition of mutant B-RAF with PLX-4032 can radiosensitize B-Raf+ melanoma cells.Methods and Materials-A large collection of melanoma cell lines (n=37) were treated with 0 -8 Gy IR and clonogenic survival assays used to generate survival curves to rank relative radiosensitivities among the cell lines. The ability of a B-RAF inhibitor, PLX-4032, to radiosensitize highly radioresistant, B-Raf+ cells was also assessed by clonogenic cell survival and spheroid invasion assays and the effects of treatment on the cell cycle assessed by FACS. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Results-MelanomaConflict of Interest Statement: The authors declare no conflicts of interest exist. NIH Public Access

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Role of brachytherapy in malignant melanoma: A preliminary report

Chadha

Hilaris

Nori

et al. 1990

Journal of Surgical Oncology

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From August 1979 to May 1986, various brachytherapy techniques were applied at Memorial Sloan Kettering Cancer Center (MSKCC) in an adjuvant setting with/without surgery and external radiation therapy in the management of advanced malignant melanoma. Thirty-three patients underwent brachytherapy procedures. The patients' ages ranged from 35 to 82 years, with a median age of 56 years. Fourteen patients had disease localized to the implant site, whereas 19 patients also had disseminated disease elsewhere. The indications for implant were residual gross disease (21), microscopically positive margins (3), and histologically negative but clinically close margins of resection (9). Local control at the implant site was noted in 80% of patients at 6 months and 42% of patients at 1 year; two patients had reached 54 months and 72 months with no evidence of disease. Local control was 100% (9/9) in patients with histologically negative but clinically close margins of resection, and 48% (11/23) with microscopically positive margins and/or gross residual disease. Complications were seen as follows: delay in wound healing (1), wound infections (4), radiation enteritis (1), small bowel obstruction (1). The present study suggests that brachytherapy combined with surgery can achieve a good local control in patients with negative but clinically close margins of resection. In patients with gross residual disease who are at a high risk for local recurrence, approximately one-half can be locally controlled with this approach. These preliminary results should be tested in a prospective controlled study.

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Broad-Shouldered Survival Curves of a Human Melanoma Xenograft Implications for radiation therapy in the absence and presence of misonidazole

Cited by 16 publications

References 27 publications

BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy

BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy

Melanoma cells show a heterogeneous range of sensitivity to ionizing radiation and are radiosensitized by inhibition of B-RAF with PLX-4032

Role of brachytherapy in malignant melanoma: A preliminary report

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