Hypoxic versus normoxic external-beam irradiation of cervical carcinoma combined with californium-252 neutron brachytherapy. Comparative treatment results of a 5-year randomized study.

PURPOSE: The article focuses on the treatment and protective effects of hypoxyradiotherapy during external-beam irradiation of cervical carcinoma, including paraaortic lymph nodes, combining radiotherapy with californium-252 ((252)Cf) neutron brachytherapy. An analysis of treatment results, early and late side effects and complications is presented. PATIENTS AND METHODS: From January 1989 to May 1997, 307 women with stage IIb and IIIb cervical carcinoma, treated with (252)Cf neutron brachytherapy, were randomly divided into two groups and treated with external-beam irradiation to the paraaortic lymph nodes as follows: 155 patients (59 with stage IIb, 96 with stage IIIb) were treated by external-beam irradiation administered as a 60-Gy dose applied under conditions of acute hypoxia; 77 patients (30 with stage IIb and 47 with stage IIIb) received extended-field irradiation up to L4 and 78 patients (29 with stage IIb and 49 with stage IIIb) up to T12. 152 patients (58 with stage IIb, 94 with stage IIIb) were treated by external-beam irradiation administered as a 40-Gy dose applied under normal oxygenation conditions. 73 patients (29 with stage IIb and 44 with stage IIIb) received extended-field irradiaton up to L4 and 79 patients (29 with stage IIb and 50 with stage IIIb) up to T12. The same 56 Gy-equivalent (eq) doses at point A and 19 Gy-eq doses at point B were applied intracavitarily in both groups. The total radiation doses at points A and B were 99 and 79 Gy-eq, respectively, for patients treated with external-beam irradiation to 60 Gy under conditions of acute hypoxia. For patients treated with external-beam irradiation to 40 Gy under normal oxygenation conditions, the doses at points A and B were 85 and 59 Gy-eq, respectively. RESULTS: The 5-year overall survival rate for all patients (stages IIb and IIIb) was 7.0% better for patients treated in acute hypoxia than for patients treated under normal oxygenation conditions (78.7% vs. 71.7% [p < 0.16]). The 5-year metastases-free survival rate was better by 11.7% for stage IIIb patients in the hypoxyradiotherapy group with extended field up to T12 as compared to patients with extended field up to L4 (97.4% vs. 85.7% [p < 0.05]). Comparison of metastases-free survival rate of stage IIIb patients after external-beam irradiation with extended field up to T12 in hypoxic condition versus normoxic condition showed a 12% better result for patients in hypoxic condition (97.4% vs. 85.4% [p < 0.04]). Occurrences of symptomatic radiation-induced reactions during or shortly after irradiation were more frequently observed in patients treated with a lower dose under normoxic conditions. During the period of 6-12 years after treatment there were no changes in the frequencies of occurrences of late effects and complications. CONCLUSION: The importance of the protective effects of hypoxyradiotherapy for dose escalation in external-beam irradiation of cervical carcinoma, including paraaortic lymph nodes, with regard to an improvement of the cure rates of metastases in paraaortic lymph nodes has been confirmed.

Californium-252 (252Cf) versus conventional gamma radiation in the brachytherapy of advanced cervical carcinoma long-term treatment results of a randomized study.

BACKGROUND: When photon radiotherapy is applied to cervical carcinoma, it has been observed that, despite important progress in radiotherapy technique and quality assurance, no significant increase in curative rates has resulted. Among the reasons for this is the varying radiosensitivity of different tumor subpopulations. Treatment with californium-252 ((252)Cf), as a source of gamma/neutron radiation in brachytherapy, provides properties and new treatment modalities that help to overcome this factor. PATIENTS AND METHODS: From January 1985 to June 1993, 227 women with stage IIB and IIIB cervical carcinoma were treated in a randomized brachytherapy study as follows: (1) 117 patients (55 with stage IIB, 62 with stage IIIB) were treated with (252)Cf during the 1st week of therapy by 6 Gy (40 Gy-eq) of the neutron component in point A. Supplementation by a 16-Gy dose with (226)Ra or (137)Cs was done in the 5th week. (2) 110 patients (50 with stage IIB, 60 with stage IIIB) were treated solely by gamma radiation ((226)Ra or (137)Cs). A dose of 56 Gy in point A was applied in two fractions at the 3rd and 5th week, respectively. The dose of 56 Gy-equivalents was completed by external radiation with 40 Gy. The total radiation doses at points A and B amounted to 85 Gy and 59 Gy, respectively. The treatment results were compared. RESULTS: The overall 5-year survival rate for all stages IIB and IIIB was better by 18.9% for (252)Cf patients than for patients receiving conventional treatment (75.2% vs. 56.3%, respectively; p < 0.001). In the stage IIIB (252)Cf group, it was significantly better by 22.8% than for the conventional group (66.1% vs. 43.3%, respectively; p < 0.003). The higher survival rate in (252)Cf patients was the result of significantly less local relapses compared with patients treated conventionally (12,8% vs. 31.8%; p < 0.0009). CONCLUSION: The importance of neutron source (252)Cf in the brachytherapy of cervical carcinoma by overcoming the tumor resistance to conventional photon irradiation has been confirmed.