High-dose-rate versus low-dose-rate intracavitary brachytherapy for carcinoma of the cervix

High-dose-rate (HDR) remote afterloading intracavitary brachytherapy has been widely used in the treatment of carcinoma of the cervix in Europe and Asia since the 1960's. Recently, there has been an increase of interest in the use of this technique in North America. Most of the non-randomized studies suggest similar survival, local control, and complication rates using fractionated high-dose-rate remote afterloading intracavitary brachytherapy combined with external beam irradiation compared to historical or concurrent low-dose-rate (LDR) controls. However, the techniques as well as the dose fractionation schedules used in different institutions are variable. The optimal technique and dose fractionation scheme has yet to be established through systematic clinical trials.     

High-dose-rate intracavitary irradiation in the treatment of carcinoma of the uterine cervix: early experience with 84 patients

Eighty-four patients with previously untreated invasive carcinoma of the uterine cervix were treated by high-dose-rate intracavitary irradiation using a remotely controlled afterloading system (Ralstron) with or without external irradiation at the National Cancer Center Hospital, Tokyo, between 1977 and 1981. Survival rates and local control rates were comparable to those for 372 patients treated by low-dose-rate intracavitary irradiation with or without external irradiation from 1972 to 1981 at the hospital. The incidence of major complications was 5.1 and 2.4% for the patients treated by low-dose-rate intracavitary irradiation and by high-dose-rate irradiation, respectively. The results are comparable to those reported by other institutions. We have abandoned the conventional low-dose-rate intracavitary irradiation with the impression that the high-dose-rate remotely controlled afterloading system is a good alternative to the conventional one.     

High-dose-rate remote afterloading intracavitary radiation therapy for cancer of the uterine cervix. A 20-year experience.

Retrospective analysis was performed on 1022 patients with squamous cell carcinoma of the uterine cervix who were treated with high-dose-rate remote afterloading intracavitary irradiation at the National Institute of Radiological Sciences, Angawa, Chiba-shi, Japan, from 1968 to 1982 in comparison with low-dose-rate intracavitary radiation therapy. The patient population consisted of 147 patients with Stage I disease, 256 patients with Stage II disease, 515 patients with Stage III disease, and 104 patients with Stage IV disease. Absolute 5-year survival rates for Stages Ib, IIa, IIb, IIIb, IVa, and IVb disease were 88.1%, 76.9%, 67.0%, 52.2%, 24.1%, and 13.3%, respectively. The rates of severe complication of Grades 3 and 4 were 4.1% for the rectosigmoid colon, 1.2% for the bladder, and 1.1% for the small intestine. In the case of Stage I to II disease, the optimal dose from intracavitary sources was suggested to be 2900 cGy +/- 200 cGy at point A, with 4 to 5 fractions of 600 to 700 cGy delivered over 4 to 5 weeks. These results suggested that high-dose-rate intracavitary radiation therapy provided clinical results comparable to those of a low-dose-rate technique.     

High-dose-rate afterloading brachytherapy in carcinoma of the uterine cervix

The Brachytron has been used in the University of California at San Diego Medical Center since 1970 as one method of treating gynecological malignancies. This machine contains a high intensity cobalt 60 remote afterloading cycling source used for intracavitary brachytherapy. One hundred twenty-seven patients with epithelial carcinoma of the cervix are available for analysis of 5-year survival, and 176 are analyzed for treatment complications two years following therapy. Five year survival figures for FIGO-staged patients treated with external beam pelvic irradiation and intracavitary Brachytron treatments are as follows: Stage I, 89%; Stage II, 58%; Stage III, 33%, and two of five patients Stage IVa. Rectal complications graded moderate or severe (M, S) were dose-related and gradually decreased over the years as techniques improved. Complications from early results in 1970-1972 (24% M, 10% S) were reduced to lower levels in 1976-1979 (14% M, 4% S). The Brachytron offers the advantage of rapid dose delivery. Thus, patients can be treated in an outpatient setting, avoiding the cost of hospitalization and the risks of anesthesia. The Brachytron also offers virtually complete radiation safety to all attending medical personnel. With survival and complication figures similar to those reported for patients treated with conventional low-dose-rate brachytherapy, the Brachytron represents an effective alternate mode of therapy for uterine carcinoma.     

Dose equivalence for high-dose-rate to low-dose-rate intracavitary irradiation in the treatment of cancer of the uterine cervix

By comparing the incidence of major radiation injury, we estimated doses clinically equivalent for high-dose-rate (HDR) to conventional low-dose-rate (LDR) intracavitary irradiation in patients with Stages IIb and IIIb cancer of the uterine cervix. We reviewed a total of 300 patients who were treated with external beam therapy to the pelvis (50 Gy in 5 weeks) followed either by low-dose-rate (253 patients) or high-dose-rate (47 patients) intracavitary treatment. The high-dose-rate intracavitary treatment was given 5 Gy per session to point A, 4 fractions in 2 weeks, with a total dose of 20 Gy. The low-dose-rate treatment was given with one or two application(s) delivering 11-52 Gy to the point A. The local control rates were similar in both groups. The incidence of major radiation injury requiring surgical intervention were 5.1% (13/253) and 4.3% (2/47) for low-dose-rate and high-dose-rate groups, respectively. The 4.3% incidence corresponded to 29.8 Gy with low-dose-rate irradiation, thus, it was concluded that the clinically equivalent dose for high-dose-rate irradiation was approximately 2/3 (20/29.8) of the dose used in low-dose-rate therapy.     

Design of intracavitary microwave applicators for the treatment of uterine cervix carcinoma

A 915 MHz intracavitary applicator was designed to heat tumours in the cervical and upper vaginal regions. The applicator has a 3.5-turn helical coil wound around the distal 19 mm of a dielectric rod 43 mm long and 30 mm in diameter. For treating uterine cancer, a 2450 MHz, 4 mm diameter helical applicator was made by replacing 6 cm of the outer conductor of a coaxial cable with six turns of copper wire soldered to the outer conductor. The heating patterns were determined thermographically in a muscle phantom. The maximum heating rates were 0.42 and 0.83 degrees C/W-min, respectively, for the 915 and 2450 MHz applicators. Intracavitary temperature distributions in the upper vagina, cervix and uterus were measured at the surface of the applicators with thermocouples. The average temperature was 46.0 +/- 2.1 degrees C (S.D.) at mid-tumour and 44.5 +/- 0.8 degrees C at the tumour periphery. The maximum temperature, up to 51.5 degrees C, was measured at the surface of the cervical applicator. The majority of the patients (28/30) tolerated the investigational treatment without burns or pain. Rectal temperatures were also monitored. The location of the hot-spot (40.7 degrees C) in the rectum, 5-7 cm above the anus, corresponded to the tip of the cervical applicator (47.1 degrees C).     

Design of intracavitary microwave applicators for the treatment of uterine cervix carcinoma

A 915 MHz intracavitary applicator was designed to heat tumours in the cervical and upper vaginal regions. The applicator has a 3.5-turn helical coil wound around the distal 19 mm of a dielectric rod 43 mm long and 30 mm in diameter. For treating uterine cancer, a 2450 MHz, 4 mm diameter helical applicator was made by replacing 6 cm of the outer conductor of a coaxial cable with six turns of copper wire soldered to the outer conductor. The heating patterns were determined thermographically in a muscle phantom. The maximum heating rates were 0.42 and 0.83°C/W-min, respectively, for the 915 and 2450 MHz applicators. Intracavitary temperature distributions in the upper vagina, cervix and uterus were measured at the surface of the applicators with thermocouples. The average temperature was 46.0 ± 2.1°C (S. D.) at mid-tumour and 44.5 ± 0.8°C at the tumour periphery. The maximum temperature, up to 51.5°C, was measured at the surface of the cervical applicator. The majority of the patients (28/30) tolerated the investigational treatment without burns or pain. Rectal temperatures were also monitored. The location of the hot-spot (40.7°C) in the rectum, 5–7 cm above the anus, corresponded to the tip of the cervical applicator (47.1°C).     

High-dose rate intracavitary therapy for carcinoma of the uterine cervix: I. General figures of survival and complication

From August 1978 through December 1982, a total of 200 patients with previously untreated carcinoma of the uterine cervix were treated using remote afterloading high-dose rate intracavitary therapy (RALS) at our department. According to the staging of UICC (1978), 8 patients were classified into Stage Ia, 22 Ib, 22 IIa, 53 IIb, 85 III, and 10 IV. Actuarial 5-year survival rates by Stage were 100% in Stage Ia, 86% Ib, 67% IIa, 72% IIb, 41% III, and 20% IV (p = 0.0001). Significant prognostic factors in Stage II were the value of hemoglobin (p = 0.0115) and age (p = 0.0431) by logrank test. Corresponding factors in Stage III were the value of hemoglobin (p = 0.0005) and total protein (p = 0.0036). Late complications after RALS developed in 22 patients (11%), that is, rectum 14 (7%), bladder 6 (3%), small intestine 4 (2%) and sigmoid colon 1 (1%). Severe complications requiring surgery were noted in 7 patients (4%). There was no fatal case attributable to complication. It is concluded that RALS is one of the most effective and safe means for the treatment of carcinoma of the uterine cervix based on our results.     

Split-course versus continuous pelvis irradiation in carcinoma of the uterine cervix: a prospective randomized clinical trial of the Radiation Therapy Oncology Group

In August 1980, the Radiation Therapy Oncology Group (RTOG) completed a prospective randomized clinical trial for the comparison of a split-course versus a standard continuous course of pelvic irradiation for carcinoma of the uterine cervix Stages II-B, III-A, III-B, and IV-A. The split-course consisted of 10 fractions of 250 rad each, 5 times a week, up to 2500 rad followed by a rest period of approximately 2 weeks and then another 2500 rad was given (250 X 10). The continuous course consisted of 30 fractions of 170 rad each, 5 times per week, for a total of 5100 rad. In both groups the external pelvis irradiation was followed by intracavitary brachytherapy in the uterus and vagina, with tandem-colpostat or tandem only, for a dose of 3000 rad at point A for the former, or at 2 cm from the center of the linear source for the latter. In cases where brachytherapy was not possible, a boost of external irradiation with reduced field, with a dose of 1600 rad (200 X 8) was advised. Three hundred and one patients were registered, of which 287 are currently evaluable. No differences between the treatments were detected for the following study end-points: treatment tolerance in terms of acute normal tissue reactions and completion of therapy, tumor control in the pelvis, severe late normal tissue reactions, and survival. In the entire study population the estimated tumor control in the pelvis at two years after initiation of therapy was: 81% for Stage II-B, 67% for III-A, 53% for Stage III-B, and 32% for Stage IV-A. The estimated two-year survival was: 70% for Stage II-B, 58% for III-A, 46% for III-B, and 23% for IV-A.     

High versus low dose rate intracavitary irradiation for adenocarcinoma of the uterine cervix.

BACKGROUND: Traditionally, low dose rate (LDR) brachytherapy has been used as a standard modality in the treatment of patients with carcinoma of the uterine cervix. The purpose of this work was to evaluate the effects of high dose rate (HDR) brachytherapy on patients with adenocarcinoma of the uterine cervix and to compare them with the effects of LDR brachytherapy. METHODS: From January 1971 to December 1992, 104 patients suffering from adenocarcinoma of the uterine cervix were treated with radiation therapy in the Department of Radiation Oncology, Yonsei University. LDR brachytherapy was carried out on 34 patients and HDR brachytherapy on 70 patients. In the LDR group, eight patients were in stage IB, six in IIA, 12 in IIB, three in IIIA and five in IIIB. External radiation therapy was delivered with 10 MV X-rays, 2 Gy fraction per day, total dose of whole pelvis 36-52 Gy (median 46 Gy). LDR radium intracavitary irradiation was performed with a Henschke applicator, 37-59 Gy targeted at point A (median 43 Gy). In the HDR group, there were 16 patients in stage IB, six in IIA, 32 in IIB and 16 in IIIB. The total whole pelvis dose of external radiation was 40-50 Gy (median 44 Gy), daily 1.8-2.0 Gy. HDR Co-60 intracavitary irradiation was performed with a remotely controlled after-loading system (RALS), 30-48 Gy (median 39 Gy) targeted at point A, three times per week, 3 Gy per fraction. RESULTS: The 5-year overall survival rate in the LDR group was 72.9, 61.9 and 35.7% in stage I, II and III, respectively and the corresponding figures for HDR were 87.1, 58.3 and 43.8% (p > 0.05). There was no statistical difference between the HDR group and the LDR group in terms of the 5-year overall survival rate from adenocarcinoma of the uterine cervix. There was a late complication rate of 12% in the LDR group and 27% in the HDR group. The incidence of late complications in stages II and III was higher in the HDR group than in the LDR group (31.6 vs 16.7% in stage II, 37.3% vs 12.5% in stage III, p > 0.05). No prognostic factors were evident in the comparison between the two groups. CONCLUSION: There was no difference in terms of 5-year survival rate in the patients with adenocarcinoma of the uterine cervix between those treated with HDR and those treated with LDR brachytherapy. Even though late complication rates were higher in the HDR group, most of them were classified as grade I. This retrospective study suggests that HDR brachytherapy may be able to replace LDR brachytherapy in the treatment of adenocarcinoma of the uterine cervix.     

Gastrointestinal complications caused by high-dose-rate intracavitary irradiation of carcinoma of the uterine cervix

We treated 64 patients with carcinoma of the uterine cervix with high-dose-rate intracavitary irradiation between 1978 and 1984. Of the 52 patients who were followed for more than two years, gastrointestinal complications occurred in 11 (21%): six grade I patients (12%), two grade II patients (4%) and three grade III patients (6%). The patients were graded according to the severity of the complications. The three patients with grade III complications underwent emergency surgery because of ileus or perforation of the gastrointestinal tract. It is suggested that these severe complications are liable to occur in patients given more than seven fractions of intracavitary irradiation in a fraction dose of 6 Gy to point A or previously operated on in the pelvic cavity. Accurate center shield in relation to tandem sources is also emphasized.     

Long-term results of high-dose rate intracavitary brachytherapy for squamous cell carcinoma of the uterine cervix

BACKGROUND: The authors performed a long-term follow-up study to evaluate the efficacy and late toxicity of high-dose rate intracavitary brachytherapy (HDR-ICBT) for cervical carcinoma. METHODS: From 1968 to 1986, 1148 patients with Stage IB to IVB squamous cell carcinoma of the cervix (staging was performed according to the International Federation of Gynecology and Obstetrics) were treated with a combination of external beam radiotherapy (EBRT) and HDR-ICBT. For patients with early-stage disease, 20 gray (Gy) of EBRT was delivered to the whole pelvis, followed by 24 Gy/4 fractions of HDR-ICBT and 30 Gy of central-shielding EBRT. For patients with advanced-stage disease, 20-40 Gy of whole pelvic EBRT was administered, followed by 24 Gy/4 fractions of ICBT and 30-10 Gy of central-shielding EBRT. The overall treatment time was approximately 6 weeks. Among survivors, the follow-up rate was 98% and the median follow-up duration was 22 years. RESULTS: The 10-year pelvic tumor control rates were 93% for patients with Stage IB disease, 82% for patients with Stage II disease, and 75% for patients with Stage III disease. The 10-year overall and cause-specific survival rates were 74% and 89% for patients with Stage IB disease, 52% and 74% for patients with Stage II disease, and 42% and 59% for patients with Stage III disease, respectively. The 10-year actuarial rates of major complications were 4.4% in the rectosigmoid colon, 0.9% in the bladder, and 3.3% in the small intestines. CONCLUSIONS: The results of the current study suggest that the combination of EBRT and HDR-ICBT according to the authors' protocol provided outcomes that were comparable to those of the conventional low-dose rate brachytherapy with acceptable rates of late complications in the treatment of cervical carcinoma.     

Radiotherapy for carcinoma of the uterine cervix by remotely controlled afterloading intracavitary system with high-dose-rate

Between January 1978 and June 1985 seventy-nine patients with carcinoma of the uterine cervix were treated by a remotely controlled afterloading system (RALS) with high-dose-rate irradiation following external beam therapy. It was given once a week with a dose per fraction of 6 Gy to point A, 3 to 6 times, using applicators equipped with 1 Ci 60Co bead in each ovoid and two 1 Ci 60Co beads in a tandem 1 cm apart. Five-year survival rates were 85, 68, and 51 percent in Stages I, II, and III, respectively. Recurrences were noted in 12 patients (20%) with a minimum follow-up of 2 years: 4 patients in the parametrium, 2 in the central area, 5 in both the parametrium and central areas, and 5 in the para-aortic lymph node. Complications were noted in 13 patients (22%): temporary rectal bleeding in 7, stenosis of the sigmoid in 2, recto-vaginal fistula in 1, ileo-sigmoidal fistula in 1, and perforation of the intestine in 2 patients. The treatment results of the high-dose-rate schedule for RALS appear to be comparable to those of conventional low-dose-rate systems reported by others. Therefore a fraction dose of 6 Gy to point A once a week by RALS should be considered to be practical, economical, and acceptable to patients.