Targeting tumour hypoxia to improve outcome of stereotactic radiotherapy.
Acta Oncol
; 54(9): 1385-92, 2015.
Article
en En
| MEDLINE
| ID: mdl-26329662
ABSTRACT
BACKGROUND:
Hypoxia is a characteristic feature of solid tumours that significantly reduces the efficacy of conventional radiation therapy. In this study we investigated the role of hypoxia in a stereotactic radiation schedule by using a variety of hypoxic modifiers in a preclinical tumour model. MATERIAL ANDMETHODS:
C3H mammary carcinomas were irradiated with 3 × 15 Gy during a one-week period, followed three days later by a clamped top-up dose to produce a dose response curve; the endpoint was tumour control. The hypoxic modifiers were nimorazole (200 mg/kg), nicotinamide (120 mg/kg) and carbogen (95% O2 + 5% CO2) breathing, OXi4503 (10 mg/kg), and hyperthermia (41.5°C; 1 h).RESULTS:
The radiation dose controlling 50% of clamped tumours (TCD50) following 3 × 15 Gy was 30 Gy. Giving nimorazole or nicotinamide+ carbogen prior to the final 15 Gy fraction non-significantly (χ(2)-test; p < 0.05) reduced this TCD50 to 20-23 Gy; when administered with each 3 × 15 Gy fraction these values were significantly reduced to ≤ 2.5 Gy. Injecting OXi4503 or heating after irradiating significantly reduced the TCD50 to 9-12 Gy regardless of whether administered with one or all three 15 Gy fractions. Combining OXi4503 and heat with the final 15 Gy had a significantly larger effect (TCD50 = 2 Gy).CONCLUSIONS:
Clinically relevant modifiers of hypoxia effectively enhanced an equivalent stereotactic radiation treatment confirming the importance of hypoxia in such schedules.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Hipoxia de la Célula
/
Radiocirugia
/
Neoplasias Mamarias Experimentales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Acta Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2015
Tipo del documento:
Article
País de afiliación:
Dinamarca