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The gold treatment for local invasive cutaneous squamous cell carcinoma is surgical excision. Nevertheless, surgery is not always an option as a consequence of the age and/or the health status of the patient. One of the objectives of this study is to assess the effects of cisplatin concomitantly with a subsequent low-energy X-rays irradiation in vitro. In order to enhance the effectiveness of this combined treatment, the temporal fractionation of the platinated compound is expected to be performed.
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Cutaneous squamous cell carcinoma (cSCC) accounts for the 20% of the most common skin malignancies, i.e. the non-melanoma skin cancer. cSCC is considered one public health problem because of the high costs of its treatment as cSCC are increasing due to a higher sun exposure, as well as more efficient dermatological examinations. In addition, this kind of skin cancer is characterized by a relatively high risk of metastasis.
The gold standard treatment for local invasive cSCC is based on the surgical excision, leading to a 5-years control rate in low-risk patients of 96%. Nevertheless, surgery for local invasive cSCC is not always an option as a consequence of the age and/or the poor health status of the patient. Therefore, ionizing radiation is used as either primary or adjuvant therapy against cSCC in elderly patients or when surgery would be extremely invasive. Although radiotherapy seem to be a promising option, it needs to be improved in order to damage locally the tumor area, thus avoiding damaging secondary effects on healthy tissues. Typical skin radiation sources are based on superficial, orthovoltage X-rays (XR) beams, as well as electron-beam therapy.
In particular, irradiations of local invasive cSCC by using a superficial XR source at kilovoltage (kV) energy permit a local dose deposition within the tumor volume, with a significant smaller penetration capacity with respect to the higher-energy XR sources. Therefore, kV XR sources become a perfect tool for the treatment of superficial lesions, such as the cSCC. The combination of these keV-energy photons with metallic atoms localized in the tumor would enhance the dose deposited locally in the target, improving thus the therapeutic index of the treatment. Among all the chemotherapeutic options available, platinum-based agents, such as cis-diamminedichloroplatinum (II) (cisplatin or cisPt) has become an essential anti-cancer drug with a substantial therapeutic impact against the most carcinomas-like tumors.
The distortion of the structure of the DNA duplex, converts cisPt in a highly toxic agent per se because of its influence on DNA replication, apoptotic death, and inhibition of the major nuclear repair pathway of cisPt-DNA adducts and radiation-induced DNA breaks. However, dose administration is a key limitation due to the high toxicity of this agent. It is for this reason that the lowest cisPt concentration was used in this study, and the expected effectiveness of cisPt on a cSCC cells were enhanced with a subsequent low-energy XR irradiation in an attempt to explore some new therapeutic strategies against local invasive cSCC.
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3 participants in 3 patient groups
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