EVALUATION OF THE CLINICAL USE OF HYPOXIC CELL SENSITIZERS IN RADIATION THERAPY OF MALIGNANT EPITHELIAL SKIN TUMORS

Abstract

Aim: To increase the efficacy of radiation therapy of malignant epithelial cell skin neoplasms with the use of radiation sensitizers of hypoxic tumor cells. Materials and methods: The study was performed in 517 patients with basal cell (n = 361) and squamous cell (n = 156) skin cancer, 274 (53%) of whom had T2 and 243 (47%), T3 tumors. Patients with locally advanced and metastatic tumors were excluded from the study. The following treatment modalities were used: distant gamma-therapy, short-distance radiation therapy and combined radiation therapy with the use of non-conventional dose fractioning at total local doses equal to 72–73 Gr. The sensibilization of hypoxic tumor cells to radiation therapy with metronidazole was done by targeted delivery of the drug to the tumor by means of topical application of Coletex-M drapes impregnated with metronidazole in a high concentration (up to 20 mcg/cm²). The second method of radiosensibilization of hypoxic tumor cells was based on a preliminary use of low intensity laser radiation onto the tumor. As a source this radiation, a helium neon laser was used with the power of up to 12 mVt and the wave length of 0.63 to 0.89 mcm, duration of sessions from 3 to 15 minutes. The control group comprised 192 skin cancer patients who underwent radiation therapy without the use of radiation sensitizers. Results: The use of metronidazole and low intensity laser radiation within the radiation therapy of T3 skin cancer patients, compared to the treatment without the radiation modifiers, significantly improved the immediate cure rates (full tumor regression at 1 to 1.5 months after completion of radiation) from 75.5 ± 3.1% to 89.2 ± 1.9% (р < 0.05). In the group with basal cell skin cancer that underwent radiation therapy combined with metronidazole, there was an association of its radio-modifying effect and tumor size. Short-distance roentgenotherapy of patients with T2 basal cell skin cancer and tumor size of < 4 cm was equally effective, irrespective of the use of metronidazole: the immediate cure rate was 94.8 ± 2.2% (92/97 patients) in the metronidazole group and 89.8 ± 3.9% (53/59) in the control group. With the combined radiation therapy of T2 basal skin cancer patients with the tumor size of 4–5 cm, the immediate cure rate was increased significantly from 73.2 ± 6.9% (30/42) in the control group to 88.2 ± 3.7% in the metronidazole group (67/76) (р < 0.05). With distant gamma-therapy of T3 basal cell skin cancer, this parameter was increased from 70.5 ± 6.8% (31/44) in the control group to 88.4 ± 4.8% (38/43) in the metronidazole group (р < 0.05). The radiation-sensitizing effect of metronidazole and low intensity laser combined with the distant gamma-therapy of T3 basal cell skin cancer was significant and similar: the immediate cure rate with the use of metronidazole was 85.9 ± 4.6% (49/57), and with the use of low intensity laser, 84.6 ± 5.0% (44/52), compared to 66.0 ± 6.9% (31/47) in the control group (р < 0.05). Although the relapse rate after radiation therapy with metronidazole or low intensity laser was lower by 5–11%, compared to that after the radiation without modifiers, there was no statistically significant difference after a 3-year follow-up. Conclusion: A significant benefit of radiation therapy combined with radiation sensitizers on the immediate cure rate of locally-advanced basal cell skin cancers was confirmed. It seems that radiation sensitizers of hypoxic cells do improve immediate results of cure without any significant effect on tumor relapse rate in the future.