Comparing radiotherapy with or without intracavitary hyperthermia in the treatment of primary nasopharyngeal carcinoma: a retrospective analysis.

AIMS AND BACKGROUND: A retrospective study was performed to evaluate the contribution of intracavitary hyperthermia in patients with nasopharyngeal carcinoma who received radiation therapy. METHODS AND STUDY DESIGN: Patients with nasopharyngeal carcinoma were treated with radiotherapy alone or with radiotherapy plus hyperthermia of the primary tumor. All patients were treated in a uniform fashion by definitive-intent radiotherapy in both groups. In the radiotherapy plus hyperthermia group, patients were treated with microwave heating hyperthermia delivered twice a week in combination with radiation. RESULTS: Between November 1992 to September 1994, 225 patients were recruited, with 98 patients matched to the criteria of either treatment group (49 in the radiotherapy and 49 in the radiotherapy plus hyperthermia group). Ninety-eight patients were included in the treatment response and 87 patients in the survival analysis according to the intent-to-treat principle (11 patients were lost to follow-up). Overall survival did not show a significant difference between the two groups (81 vs 86 months of median survival time, respectively, P = 0.068). However, there were significant differences not only in progression-free survival (median months, 60 vs 100, respectively, P = 0.036), but also in local progression-free survival (median months, 54 vs 111, respectively, P = 0.029) between the radiotherapy and radiotherapy plus hyperthermia groups. No statistical difference was noted in the cumulative incidence of grade 3 adverse events or late radiation morbidity during follow-up between the two study groups. CONCLUSIONS: The retrospective study showed that hyperthermia combined with radiation therapy can improve progression-free survival and local progression-free survival, although no increase in overall survival was observed. Thus, the inclusion of hyperthermia in the treatment of nasopharyngeal carcinoma using radiation offers no survival benefit but may help to improve the current standard of care consisting of radiation and chemotherapy.

Synergistic effect of combination topotecan and chronomodulated radiation therapy on xenografted human nasopharyngeal carcinoma.

PURPOSE: To investigate the in vivo chronomodulated radiosensitizing effect of topotecan (TPT) on human nasopharyngeal carcinoma (NPC) and its possible mechanisms. METHODS AND MATERIALS: Xenografted BALB/c (nu/nu) NPC mice were synchronized with an alternation of 12 hours of light from 0 to 12 hours after light onset (HALO) and 12 hours of darkness to establish a unified biological rhythm. Chronomodulated radiosensitization of TPT was investigated by analysis of tumor regrowth delay (TGD), pimonidazole hydrochloride, histone H2AX phosphorylation, (γ-H2AX) topoisomerase I (Top I), cell cycle, and apoptosis after treatment with (1) TPT (10 mg/kg) alone; (2) radiation therapy alone (RT); and (3) TPT+RT at 3, 9, 15, and 21 HALO. The tumor-loaded mice without any treatment were used as controls. RESULTS: The TPT+RT combination was more effective than TPT or RT as single agents. The TPT+RT combination at 15 HALO was best (TGD = 58.0 ± 3.6 days), and TPT+RT at 3 HALO was worst (TGD = 35.0 ± 1.5 days) among the 4 TPT+RT groups (P<.05). Immunohistochemistry analysis revealed a significantly increased histone H2AX phosphorylation expression and decreased pimonidazole hydrochloride expression in the TPT+RT group at the same time point. The results suggested that the level of tumor hypoxia and DNA damage varied in a time-dependent manner. The expression of Top I in the TPT+RT group was also significantly different from the control tumors at 15 HALO (P<.05). Cell apoptosis index was increased and the proportion of cells in S phase was decreased (P<.05) with the highest value in 15 HALO and the lowest in 3 HALO. CONCLUSIONS: This study suggested that TPT combined with chronoradiotherapy could enhance the radiosensitivity of xenografted NPC. The TPT+RT group at 15 HALO had the best therapeutic effect. The chronomodulated radiosensitization mechanisms of TPT might be related to circadian rhythm of tumor hypoxia, cell cycle redistribution, DNA damage, and expression of Top I.