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


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.


CONCLUSIONS
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.
Tacev
Taco
T
Masaryk Memorial Cancer Institute, Brno, Czech Republic. tacevovi@volny.cz
Vacek
Antonín
A
Ptácková
Blanka
B
Strnad
Vratislav
V
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy; D000328:Adult; D000368:Aged; D001918:Brachytherapy; D002142:Californium / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy; D015687:Cell Hypoxia; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009502:Neutrons / Q000009:adverse effects / Q000627:therapeutic use; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000628:therapy*
D002142:Californium