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.

Remote afterloading for neutron brachytherapy using californium-252.

BACKGROUND: Despite a pronounced technical process attained in radiotherapy of malignant neoplasms, no remarkable improvement in the treatment results has been achieved. The reason for this stagnation is the interaction between tumor cell and photon radiation. Tumor resistance against photon bombardment can be broken down by applying high linear energy transfer (LET) radiation-based treatment. The discovery of californium-252 ((252)Cf) nuclide, a source of gamma neutron radiation, established a precondition for using neutrons in tumor brachytherapy. The design of a remote afterloading device using (252)Cf sources remains an unsolved problem. MATERIAL AND METHODS: The afterloading device has been designed as a stationary radiator which is composed of three mutually interconnected units: 1. the control and drive unit consisting of a control computer and a motor-driven bowden system carrying the (252)Cf source; 2. the source which is housed in a watertight concrete vessel-storage strong room, situated in the ground at a depth of 25 cm beneath the patient's bed; 3. the afterloading application module installed in the irradiation room. RESULTS: Remote afterloading allows simple, inexpensive and highly efficient radiation protection and work safety for the operating personnel. The sources may be moved arbitrarily during treatment with a position accuracy of 0.5-1.0 mm within a distance of 520 cm from the source storage position in the strong room to the application position. Both afterloading systems' unused indexer outputs are protected electronically and mechanically against any unintentional movement of the source outside the application tubes. CONCLUSION: The technologic concept of the present automatic afterloading device for neutron brachytherapy represents a possible option from the range of conceivable design variants, which - while minimizing technologic and economic requirements - provides the operating personnel with optimum protection and work safety, thus extending the applicability of high LET radiation-based treatment methods in clinical practice.

Preoperative hypoxyradiotherapy of colorectal carcinoma.

AIM: The article focuses on the radioprotective effect of acute hypoxia on healthy tissues during preoperative accelerated hypoxyradiotherapy of colorectal carcinoma performed as locoregional irradiation including the common iliac lymph nodes. Analysis of early and late side effects and complications. PATIENTS AND METHODS: In this prospective study, early and late complications were assessed in 50 patients as a function of hypoxyradiotherapeutic dose increase. The preliminary treatment results of this radiotherapeutic modification were evaluated after a median follow-up of 48 months using Kaplen-Meier analysis. Between April 1991 and February 1997, 50 patients (36 men and 14 women) with colorectal carcinoma were treated preoperatively with locoregional accelerated hypofractionated hypoxyradiotherapy. The extent of disease was classified according to Dukes' criteria (A: four patients, B. 28 patients, C: 18 patients). We used a 20-MeV linear accelerator with two parallel opposed fields. Hypoxyradiotherapy was performed extending from the perineum to the L4 region. Acute hypoxia was induced during irradiation by ventilation of a hypoxic gas mixture containing 7.8-8.0% oxygen. Total doses of 24 Gy/8 days, 28 Gy/9 days, and 32 Gy/10 days were applied in five, 20, and 25 patients, respectively. Low anterior resection or abdominoperineal amputation of the rectum was performed the day after completion of preoperative hypoxyradiotherapy. The early reactions after irradiation were evaluated according to the Common Toxicity Criteria of the National Cancer Institute (CTC-NCI). RESULTS: Early postirradiation proctitis was documented in three and early radiation-induced cystitis in two patients only. Neither early nor late radiation-associated complications were observed in any of the three hypoxyradiotherapy schedules during the follow-up period of 6-105 months. Based on Kaplan-Meier analysis (median 48 months), a 5-year overall survival rate of 61.5% and a local relapse-free survival rate of 84.2% can be expected. Treatment failures were predominantly systemic. CONCLUSION: We believe it can be concluded that acute hypoxia has a radioprotective effect on normal tissues during accelerated hypoxyradiotherapy of colorectal carcinoma. Hypoxyradiotherapy permits safe administration of doses higher than those tolerated by normoxic, noncanceorus tissue, resulting in the amplification of the biological effect of radiation on tumor tissue and contributing to an improved outcome after combined radiosurgical treatment of colorectal carcinoma.