High-dose-rate afterloading brachytherapy in carcinoma of the cervix: an experience of 1992 patients

Purpose: To report the results of radiation therapy in carcinoma of the cervix treated by external irradiation and high-dose-rate (HDR) intracavitary brachytherapy.

Methods and Materials: This is a retrospective analysis of 2063 patients with histologically proven carcinoma of the cervix treated by external irradiation and HDR intracavitary brachytherapy between March 1985–December 1991. The Kaplan-Meier method was used for survival and disease-free survival analysis. Late complications in the bowel and bladder were calculated actuarially.

Results: There were 71 patients who did not complete the course of irradiation so only 1992 patients were retrospectively analyzed for survival. There were 2 patients (0.1%) in Stage IA, 211 (10.2%) Stage IB, 225 (10.9%) in Stage IIA, 902 (43.7%) in Stage IIB, 14 (0.7%) in Stage IIIA, 675 (32.7%) in Stage IIIB, 16 (0.8%) in Stage IVA, and 16 (0.8%) in Stage IVB. The median follow-up time was 96 months. The actuarial 5-year disease-free survival rate was 79.5%, 70.0%, 59.4%, 46.1%, 32.3%, 7.8%, and 23.1% for Stage IB, IIA, IIB, IIIA, IIIB, IVA, and IVB respectively. The actuarial 5-year disease-free survival rate for Stage IB₁ and IB₂ squamous cell carcinoma was 88.7% and 67.0%. The actuarial 5-year overall survival rate was 86.3%, 81.1%, 73.0%, 50.3%, 47.8%, 7.8%, and 30.8% for Stage IB, IIA, IIB, IIIA, IIIB, IVA, and IVB respectively. Pattern of failure revealed 20.8% local recurrence, 18.7% distant metastases, and 4% in both. The late complication rate Grade 3 and 4 (RTOG) for bowel and bladder combined was 7.0% with 1.9% Grade 4.

Conclusion: HDR brachytherapy used in this series produced pelvic control and survival rates comparable to other LDR series.     

High-dose-rate versus low-dose-rate brachytherapy in the treatment of cervical cancer: analysis of tumor recurrence--the University of Wisconsin experience

Purpose: To retrospectively compare the clinical outcome for cervical cancer patients treated with high-dose-rate (HDR) vs. low-dose-rate (LDR) brachytherapy.

Methods and Materials: One hundred ninety-one LDR patients were treated from 1977 to 1988 and compared to 173 HDR patients treated from 1989 to 1996. Patients of similar stage and tumor volumes were treated with identical external beam fractionation schedules. Brachytherapy was given in either 1 or 2 LDR implants for the earlier patient cohort, and 5 HDR implants for the latter cohort. For both patient groups, Point A received a minimum total dose of 80 Gy. The linear-quadratic formula was used to calculate the LDR dose-equivalent contribution to Point A for the HDR treatments. The primary endpoints assessed were survival, pelvic control, relapse-free survival, and distant metastases. Endpoints were estimated using the Kaplan-Meier method. Comparisons between treatment groups were performed using the log-rank test and Cox proportional hazards models.

Results: The median follow-up was 65 months (2 to 208 months) in the LDR group and 22 months (1 to 85 months) in the HDR group. For all stages combined there was no difference in survival, pelvic control, relapse-free survival, or distant metastases between LDR and HDR patients. For Stage IB and II HDR patients, the pelvic control rates were 85% and 80% with survival rates of 86% and 65% at 3 years, respectively. In the LDR group, Stage IB and II patients had 91% and 78% pelvic control rates, with 82% and 58% survival rates at 3 years, respectively. No difference was seen in survival or pelvic control for bulky Stage I and II patients combined (> 5 cm). Pelvic control at 3 years was 44% (HDR) versus 75% (LDR) for Stage IIIB patients (p = 0.002). This difference in pelvic control was associated with a lower survival rate in the Stage IIIB HDR versus LDR population (33% versus 58%, p = 0.004). The only major difference, with regard to patient characteristics, between the Stage IIIB patients was the incidence of hydronephrosis in the HDR vs. LDR group—28% vs. 12%, respectively (p = 0.05). For Stage IIIB patients treated with HDR, our analysis suggested that pelvic control rates improved when the first brachytherapy insertion was performed after the majority of external beam radiotherapy had been delivered.

Conclusion: Similar outcome was observed for Stage IB and II patients treated with either HDR or LDR brachytherapy—regardless of tumor volume. However, poorer survival and pelvic control rates were observed for Stage IIIB patients treated with HDR brachytherapy. If HDR is used for Stage IIIB patients, our results suggest the majority of external beam radiotherapy should be delivered prior to initiating the brachytherapy to allow for adequate tumor regression. HDR brachytherapy is more convenient for patients, decreases the radiation exposure for health care workers, and should be considered a standard therapy for women with Stage I or II cervical cancer.     

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.     

High-dose-rate versus low-dose-rate intracavitary therapy for carcinoma of the uterine cervix: a randomized trial

BACKGROUND: This was a prospective randomized clinical trial undertaken at our institution to compare low-dose-rate (LDR) intracavitary radiation therapy versus high-dose-rate (HDR) intracavitary radiation therapy for the treatment of cervical carcinoma. METHODS: From January 1984 to December 1997, a total of 132 patients with Stage II or IIIB of invasive carcinoma of the uterine cervix were entered into this randomized study. Treatment arm by HDR or LDR was allocated according to the month of each patient's birth. External irradiation consisted of whole pelvis irradiation and pelvic irradiation. Doses of external irradiation for both groups were identical. The authors used 0.588 as the conversion factor of total intracavitary dose from LDR to HDR. RESULTS: The 5-year disease specific survival rates of Stage II and III patients treated with HDR were 69% and 51% whereas those with LDR were 87% and 60%, respectively. The 5-year pelvic recurrence free survival rates of Stage II and III patients treated with HDR were 89% and 73% whereas those with LDR were 100% and 70%, respectively. There was no significant difference in disease specific survival or pelvic recurrence free survival rates between HDR and LDR. The actuarial complication rate (Radiation Therapy Oncology Group Grade 3, 4, or 5) at 5 years was 10% in the HDR group and 13% in the LDR group, and the difference between the HDR and LDR groups was not statistically significant. CONCLUSIONS: The pelvic control or actuarial complication rates were comparable between HDR and LDR treatment. The difference between the disease specific survival rates for HDR and LDR was not statistically significant for Stage II or III, although in Stage II, patients treated with LDR appeared to have a better survival rate than those treated with HDR.     

Treatment results of high-dose-rate remote afterloading brachytherapy for cervical cancer and retrospective comparison of two regimens

PURPOSE: To review the treatment results and complications of high-dose-rate (HDR) intracavitary brachytherapy for patients with carcinoma of the cervix in a single institute and to compare them with those of low-dose-rate (LDR) brachytherapy reported in the literature. METHODS AND MATERIALS: Two hundred twenty patients with carcinoma of the cervix were treated by primary radiotherapy between 1991 and 1998. The median age was 63 (range 24-84). The distribution according to Federation of Gynecology and Obstetrics (FIGO) staging system was as follows: Stage IB, 11.4%; IIA, 9.1%; IIB, 50.9%; IIIA, 3.6%; IIIB, 23.2%; and IVA, 1.8%. They were treated with whole pelvic irradiation giving 40 Gy to the midplane in 20 fractions over 4 weeks. This was followed by parametrial irradiation, giving 16-20 Gy in 8-10 fractions. HDR intracavitary brachytherapy was given weekly, with a dose of 7 Gy to point A for three fractions and, starting from 1996, 6 Gy weekly for four fractions. The median overall treatment time was 50 days (range 42-73 days). The median follow-up time was 4.7 years (range 3 months to 11.1 years). Multivariate analysis was performed using the Cox regression proportional hazards model. RESULTS: The complete remission rate after radiotherapy was 93.4% (211/226). The 5-year actuarial failure-free survival (FFS) and cancer-specific survival (CSS) rates for stage IB, IIA, IIB, IIIA, IIIB, and IVA were 87.7% and 86.6%, 85% and 85%, 67.8% and 74%, 46.9% and 54.7%, 44.8% and 50.4%, 0% and 25%, respectively. On multivariate analysis, young age (< 50) (p = 0.0054), adenocarcinoma (p = 0.0384), and stage (p = 0.0005) were found to be independent poor prognostic factors. The 5-year actuarial major complication rates (Grade 3 or above) were as follows: proctitis, 1.0%; cystitis, 0.5%; enteritis, 1.3%; and overall, 2.8%. On multivariate analysis, history of pelvic surgery was a significant prognosticator. The two HDR fractionation schedules were not a significant prognosticator in predicting disease control and complications. CONCLUSION: Our experience in treating cervical cancer with HDR intracavitary brachytherapy is encouraging. Our treatment results and complication rates were compatible with those of the LDR series. Further studies are eagerly awaited to better define the optimal fractionation schedule for HDR brachytherapy and the schedule on how chemotherapy may be combined with it.     

Comparison of low and high dose rate brachytherapy in the treatment of uterine cervix cancer. Retrospective analysis of two sequential series

PURPOSE: This retrospective analysis aims to report on the comparative outcome of cervical cancer patients treated with low dose rate (LDR) and high dose rate (HDR) brachytherapy. METHODS AND MATERIALS: From 1989 to 1995, 190 patients were treated with low dose rate (LDR) brachytherapy (LDR group) and from 1994 to 2001, 118 patients were treated with high dose rate (HDR) brachytherapy (HDR group). FIGO stage distribution for the LDR group was Stage I: 6.3%; Stage II: 57.4%; and Stage III: 36.3% and for the HDR group Stage I: 9.3%; Stage II: 43.2%; and Stage III: 47.4%. All patients were treated with telecobalt external-beam radiotherapy (EBR). Median doses of LDR brachytherapy at Point A were 40 Gy and 50 Gy for patients treated with 1 and 2 implants, respectively. All patients from the HDR group were treated with 24 Gy in 4 fractions of 6 Gy to Point A. Survival, disease-free survival, local control, and late complications at 5 years, were endpoints compared for both groups. RESULTS: Median follow-up time for LDR and HDR groups was 70 months (range, 8-127 months) and 33 months (range, 4-117 months), respectively. For all stages combined, overall survival, disease-free survival, and local control at 5 years were better in the LDR group (69% vs. 55%, p = 0.007; 73% vs. 56%, p = 0.002; and 74% vs. 65%; p = 0.04, respectively). For clinical Stages I and II, no differences was seen in overall survival, disease-free survival, and local control at 5 years between the two groups. For clinical Stage III, overall survival and disease-free survival at 5 years were better in the LDR group than in the HDR group (46% vs. 36%, p = 0.04 and 49% vs. 37%, p = 0.03, respectively), and local control was marginally higher in the LDR group than in the HDR group (58% vs. 50%, p = 0.19). The 5-year probability of rectal complications was higher in the LDR group than in the HDR group (16% vs. 8%, p = 0.03) and 5-year probability of small bowel and urinary complications was not statistically different between the the LDR group and the HDR group (4.6% vs. 8.9%, p = 0.17 and 6% vs. 3%, p = 0.13, respectively). CONCLUSIONS: This comparative series suggests similar outcome for Stages I and II patients treated with either HDR or LDR brachytherapy. Lower overall and disease-free survival and marginally lower local control were observed for Stage III patients treated with HDR brachytherapy. Less late rectal complications were observed in the HDR group patients. These findings were probably the result of the relatively low HDR brachytherapy dose delivered at Point A.     

Results and complications of high dose rate and low dose rate brachytherapy in carcinoma of the cervix: Cerrahpa?a experience.

PURPOSE: To evaluate the results and complications of treatment with high dose rate (HDR) compared to low dose rate (LDR) brachytherapy in cervical carcinoma. METHODS: Three hundred and seventy patients who were treated with external irradiation and intracavitary brachytherapy and followed for more than 2 years between 1978 and 1998 have been recently updated. The low dose rate group consisted of 77 cases treated between 1978 and 1982 and HDR group consisted of 293 cases treated between 1982 and 1998. All patients first received external irradiation with 60Co or 9-18 MV photons and a median dose of 54 Gy was given in 6 weeks. In the LDR group, intracavitary treatment was given with Manchester applicators loaded with radium (30 mg) in an intrauterine tube and 20 mg in vaginal ovoids. The dose delivered to point A was on average 32 Gy in one application. In the HDR group, a total dose of 24 Gy was given to point A in three insertions 1 week apart. The dose rate was 0.62 Gy at point A. RESULTS: The 5-year pelvic control rate was found to be 73% in the HDR group, compared with 86% in the radium group for stage I cases. In stage IIB and IIIB cases, the rates were 68% and 45% for HDR and 65% and 53% for LDR, respectively. In all stages, there was no statistical difference in pelvic control and survival rates between the two groups. Overall incidence of late complications was found as 31.1% and 31.9% in HDR and LDR groups, respectively. The grade 2-4 late complication rate was 14% in the HDR group compared to 19% in the LDR group (P>0.05). CONCLUSION: HDR brachytherapy in the management of the cervix appears to be a safe and efficacious approach. Pelvic control, survival and complications rates are quite similar when compared with LDR.     

A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma.

To clarify the role of thermoradiotherapy for FIGO Stage IIIB cervical carcinomas, both the clinical response and survival of patients treated with radio- or thermoradiotherapy were investigated. Forty patients with Stage IIIB uterine cervix carcinoma were treated with external beam irradiation to the pelvis, combined with iridium 192 high-dose-rate intracavitary brachytherapy. All patients were divided randomly into the following two groups: the radiotherapy (RT) group of 20 patients, who underwent radiotherapy alone; and the thermoradiotherapy (TRT) group of 20 patients, who underwent three sessions of hyperthermia in addition to radiotherapy. The primary endpoint of this study was local complete response and survival. A complete response was achieved in 50% (10 of 20) in the RT group versus 80% (16 of 20) in the TRT group (p = 0.048). The 3-year overall survival and disease-free survival of the patients who were treated with TRT (58.2 and 63.6%) were better than those of the patients treated with RT (48.1 and 45%), but these differences were not significant. The 3-year local relapse-free survival of the patients who were treated with TRT (79.7%) was significantly better than that of the patients treated with RT (48.5%) (p = 0.048). TRT, as delivered in this trial, was well tolerated and did not significantly add to either the relevant clinical acute or long-term toxicity over radiation alone. TRT resulted in a better treatment response and 3-year local relapse-free survival rate than RT for patients with FIGO Stage IIIB cervical carcinoma.     

A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma

To clarify the role of thermoradiotherapy for FIGO Stage IIIB cervical carcinomas, both the clinical response and survival of patients treated with radio- or thermoradiotherapy were investigated. Forty patients with Stage IIIB uterine cervix carcinoma were treated with external beam irradiation to the pelvis, combined with iridium 192 high-dose-rate intracavitary brachytherapy. All patients were divided randomly into the following two groups: the radiotherapy (RT) group of 20 patients, who underwent radiotherapy alone; and the thermoradiotherapy (TRT) group of 20 patients, who underwent three sessions of hyperthermia in addition to radiotherapy. The primary endpoint of this study was local complete response and survival. A complete response was achieved in 50% (10 of 20) in the RT group versus 80% (16 of 20) in the TRT group (p = 0.048). The 3-year overall survival and disease-free survival of the patients who were treated with TRT (58.2 and 63.6%) were better than those of the patients treated with RT (48.1 and 45%), but these differences were not significant. The 3-year local relapse-free survival of the patients who were treated with TRT (79.7%) was significantly better than that of the patients treated with RT (48.5%) (p = 0.048). TRT, as delivered in this trial, was well tolerated and did not significantly add to either the relevant clinical acute or long-term toxicity over radiation alone. TRT resulted in a better treatment response and 3-year local relapse-free survival rate than RT for patients with FIGO Stage IIIB cervical carcinoma.     

A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma

To clarify the role of thermoradiotherapy for FIGO Stage IIIB cervical carcinomas, both the clinical response and survival of patients treated with radio- or thermoradiotherapy were investigated. Forty patients with Stage IIIB uterine cervix carcinoma were treated with external beam irradiation to the pelvis, combined with iridium 192 high-dose-rate intracavitary brachytherapy. All patients were divided randomly into the following two groups: the radiotherapy (RT) group of 20 patients, who underwent radiotherapy alone; and the thermoradiotherapy (TRT) group of 20 patients, who underwent three sessions of hyper-thermia in addition to radiotherapy. The primary endpoint of this study was local complete response and survival. A complete response was achieved in 50% (10 of 20) in the RT group versus 80% (16 of 20) in the TRT group (p = 0.048). The 3-year overall survival and disease-free survival of the patients who were treated with TRT (58.2 and 63.6%) were better than those of the patients treated with RT (48.1 and 45%), but these differences were not significant. The 3-year local relapse-free survival of the patients who were treated with TRT (79.7%) was significantly better than that of the patients treated with RT (48.5%) (p = 0.048). TRT, as delivered in this trial, was well tolerated and did not significantly add to either the relevant clinical acute or long-term toxicity over radiation alone. TRT resulted in a better treatment response and 3-year local relapse-free survival rate than RT for patients with FIGO Stage IIIB cervical carcinoma.     

Effective Treatment of Stage I Uterine Papillary Serous Carcinoma with High Dose-Rate Vaginal Apex Radiation (192Ir) and Chemotherapy

Purpose: Uterine papillary serous carcinoma (UPSC) is a morphologically distinct variant of endometrial carcinoma that is associated with a poor prognosis, high recurrence rate, frequent clinical understaging, and poor response to salvage treatment. We retrospectively analyzed local control, actuarial overall survival (OS), actuarial disease-free survival (DFS), salvage rate, and complications for patients with Federation International of Gynecology and Obstetrics (FIGO) (1988) Stage I UPSC.Methods and Materials: This retrospective analysis describes 38 patients with FIGO Stage I UPSC who were treated with the combinations of radiation therapy, chemotherapy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH/BSO), with or without a surgical staging procedure. Twenty of 38 patients were treated with a combination of low dose-rate (LDR) uterine/vaginal brachytherapy using ²²⁶Ra or ¹³⁷Cs and conventional whole-abdomen radiation therapy (WART) or whole-pelvic radiation therapy (WPRT). Of 20 patients (10%) in this treatment group, 2 received cisplatin chemotherapy. Eighteen patients were treated with high dose-rate (HDR) vaginal apex brachytherapy using ¹⁹²Ir with an afterloading device and cisplatin, doxorubicin, and cyclophosphamide (CAP) chemotherapy (5 of 18 patients). Only 6 of 20 UPSC patients treated with combination LDR uterine/vaginal brachytherapy and conventional external beam radiotherapy underwent complete surgical staging, consisting of TAH/BSO, pelvic/para-aortic lymph node sampling, omentectomy, and peritoneal fluid analysis, compared to 15 of 18 patients treated with HDR vaginal apex brachytherapy.Results: The 5-year actuarial OS for patients with complete surgical staging and adjuvant radiation/chemotherapy treatment was 100% vs. 61% for patients without complete staging (p = 0.002). The 5-year actuarial OS for all Stage I UPSC patients treated with postoperative HDR vaginal apex brachytherapy and systemic chemotherapy was 94% (18 patients). The 5-year actuarial OS for Stage I UPSC patients treated with HDR vaginal apex brachytherapy and chemotherapy who underwent complete surgical staging was 100% (15 patients). The 5-year actuarial OS for the 20 Stage I UPSC patients treated with combinations of pre- and postoperative LDR brachytherapy and postop WART was 65%. None of the 6 surgically staged UPSC patients treated with LDR radiation and WART/WPRT developed recurrent disease. For patients with FIGO Stage IA, IB, and IC UPSC who underwent complete surgical staging, the 5-year actuarial DFS by depth of myometrial invasion was 100, 71, and 40%, respectively (p = 0.006). The overall salvage rate for local and distant recurrence was 0%. Complications following HDR vaginal apex brachytherapy included only Radiation Therapy Oncology Group (RTOG) grade 1 and 2 toxicity in 16% of patients. However, complications from patients treated with WART/WPRT, and/or LDR brachytherapy, included RTOG grade 3 and 4 toxicity in 15% of patients.Conclusion: Patients with UPSC should undergo complete surgical staging, and completely surgically staged FIGO Stage I UPSC patients can be effectively and safely treated with HDR vaginal apex brachytherapy and chemotherapy. Both OS and DFS of patients with UPSC are dependent on depth of myometrial invasion. The salvage rate for both local and distant UPSC recurrences is extremely poor. Complications from HDR vaginal apex brachytherapy were minimal.     

The effect of volume of disease in patients with carcinoma of the uterine cervix

This is a retrospective study of 635 consecutively treated patients with FIGO Stage IIB or IIIB carcinoma of the uterine cervix. All patients were treated definitively with radiation therapy. The effect of volume of disease on outcome was studied. The 5-, 10-, and 15-year disease-free survivals (DFS) for the 346 Stage IIB patients were 64%, 61%, and 58%, respectively. Corresponding DFS for the 289 Stage IIIB patients were 40%, 38%, and 34%, respectively. The presence of bilateral parametrial invasion did not alter the 10-year DFS in Stage IIB patients (61% vs 64%, p = 0.60) but did decrease it in Stage IIIB patients (34% vs 50%, p = 0.006). Patients with both Stage IIB and IIIB cancers and central bulky disease (greater than or equal to 5 cm in diameter) had decreased DFS when compared to those without central bulky disease. Stage IIB patients with the lateral half of the parametrium involved had a decreased 10-year DFS in comparison with medial half involvement (52% vs 68%, p = 0.004). The total pelvic failure rate was 23% for Stage IIB and 41% for Stage IIIB patients. Central bulkiness increased the pelvic failure rate by about 11% for all patients. Bilateral parametrial disease increased the pelvic failure rate in Stage IIIB patients but not in patients with Stage IIB disease. The total pelvic failure rate for Stage IIB patients was greater in those whose disease extended into the lateral parametrium. Multivariate analysis was done using stage, lateral pelvic wall dose, parametrial disease, central bulkiness, age, and total dose to point A as variables. With local control as the endpoint, only stage (IIB vs IIIB) was significant (p = 0.008). Using DFS as the endpoint, stage (p = 0.0001) and central bulkiness of tumor (p = 0.026) were significant. Complications were not increased in patients with bulky or bilateral disease. We conclude that there is justification for subdividing FIGO Stage IIIB patients into those with unilateral or bilateral disease; however, these data do not support such a division for FIGO Stage IIB patients. These latter patients would be better analyzed with reference to medial versus lateral parametrial extension because of the difference in pelvic control and survival.     

Current controversies in high-dose-rate versus low-dose-rate brachytherapy for cervical cancer

The use of brachytherapy in the treatment of cervical cancer has increased worldwide since its initial introduction over 100 years ago. However, certain aspects of the use of high-dose-rate (HDR) versus low-dose-rate (LDR) brachytherapy continue to be controversial, particularly the role of HDR in FIGO Stage III cervical cancer and the use of HDR with concurrent chemotherapy. This study represents a systematic literature review of prospective and retrospective series of patients with cervical carcinoma treated with external-beam radiation (EBRT) followed by either HDR or LDR radiation. The local control rates, survival rates, and treatment-related complications in patients with Stage III cervical cancer treated with HDR or LDR and those treated with concomitant chemotherapy are examined. Patients with Stage III cervical cancer treated with EBRT and brachytherapy have a local control rate of >50% in most series. Randomized prospective and retrospective studies show overall statistically equivalent local control, overall survival, and complication rates between HDR and LDR. However, LDR may be preferable for large, bulky tumors at the time of brachytherapy. Retrospective studies of HDR and concurrent chemotherapy are limited but have demonstrated toxicity rates similar to those with LDR. Selected patients with Stage III cervical carcinoma who have an adequate response to EBRT and concomitant chemotherapy may be treated with HDR brachytherapy. The existing literature shows no significant increase in complications in patients treated with HDR and concurrent chemotherapy; however, sufficient tumor shrinkage prior to HDR and careful monitoring of the dose to the normal tissues are imperative.     

A population-based study of cervix cancer: incidence, management and outcome in the Canadian province of Saskatchewan

Aims

To document the incidence, management and outcome of uterine cervix cancer in the Canadian province of Saskatchewan. To compare provincial results of low dose rate (LDR) and high dose rate (HDR) brachytherapy in this population.

Materials and methods

We carried out a retrospective population-based cohort study of all uterine cervix cancer cases in Saskatchewan diagnosed between 1985 and 2001. We used data from the provincial cancer registry for incident cases, the provincial death registry for vital status information and chart reviews for treatment and toxicity information.

Results

In total, 714 cases of uterine cervix cancer were identified. Stage distribution was IA 22.7%, IB 31.8%, II 19.1%, III 18.4%, IV 6.8%; 81.2% were squamous cell carcinoma, 13.4% adenocarcinoma, 1.5% adenosquamous, 0.9% small cell and 3.1% other. The annual crude incidence rate of uterine cervix cancer in Saskatchewan ranged from 6.5 to 12.3% between 1985 and 2001. The 5-year cause-specific survival rate ranged from 100% for stage IA1 to 22% for stage IV. One hundred and seven patients were treated with LDR and 37 with HDR with similar stage distribution. The 5-year cause-specific survival rate was 56% for HDR and 67% for LDR (P = 0.72). For 43 patients managed with external beam radiotherapy alone, outcome was poor for stage IIB to IIIB. The most common acute toxicities of radiation treatment were diarrhoea (60%) and abdominal cramps (12.5%). The common chronic toxicities were vaginal stenosis (5.5%) and small bowel obstruction (4%).

Conclusions

Our population-level outcomes are in keeping with published observed results and provide some of the first Canadian population-level data on HDR and LDR outcomes. We found no significant different in cause-specific survival between patients managed with HDR and LDR, although interpretation is limited by patient numbers. Our results for external beam radiotherapy alone emphasise the vital role brachytherapy plays in the management of cervical cancer.     

宫颈癌低剂量率后装腔内放射治疗的远期疗效

目的 评价Gynatron低剂量率后装腔内治疗机的疗效。方法 总结1980年4月－1986年6月间,应用Gynatron后装机配合^60Co治疗机进行根治性放疗的136例宫颈癌,并与镭疗及高剂量率腔内后装治疗进行比较分析。结果 除5例失访外,全部患者随访超过15年,随访率96.3%（131／136）。Ⅱ、Ⅲ期的10年生存率分别为83.9%和43.2%。总10年生存率为63.5%。放射性直肠炎发生率为12.5%（17／136）,放射性膀胱炎发生率9.6%（13／136）。结论 Gynatron低剂量率后装腔内治疗系统虽然有一定局限性,但仍可获得较满意的疗效;其治疗并发症患者可以接受,放射性直肠炎、放射性膀胱炎发生率高于镭疗,低于高剂量率腔内后装放疗。     

Patterns of brachytherapy practice for patients with carcinoma of the cervix (1996-1999): a patterns of care study

PURPOSE/OBJECTIVE: To analyze the details of brachytherapy practice in patients treated for carcinoma of the cervix in the United States between 1996 and 1999. METHODS AND MATERIALS: Radiation facilities were selected from a stratified random sample. Patients were randomly selected from lists of eligible patients treated at each facility. A total of 442 patients' records were reviewed in 59 facilities to obtain data about patients' characteristics, evaluation, tumor extent, and treatment. National estimates were made using weights that reflected the relative contribution of each institution and of each patient within the sampled institutions. From our survey we estimate that 16,375 patients were treated in the United States during this study period. Unless otherwise specified, brachytherapy practice was based on the 408 patients who had their brachytherapy or all their treatment at the surveyed facility. Results: A total of 91.5% of patients underwent brachytherapy at the initial treating institution; 8.5% were referred to a second site for brachytherapy. Forty-two percent of U.S. facilities referred at least some patients to a second facility for brachytherapy. Of U.S. facilities that treated < or =2 eligible patients per year, 61% referred all of their patients to a second facility for brachytherapy or treated with external RT alone; none of the U.S. facilities with larger experience (>2 eligible patients per year) referred all their patients to a second facility for brachytherapy treatment, but 28% referred some patients to an outside facility for brachytherapy. Overall, 94% of patients who completed treatment with curative intent received brachytherapy. Of these patients who had brachytherapy, 77.8%, 13.3%, and 0.9%, respectively, were treated with low-dose-rate (LDR), high-dose-rate (HDR), or a combination of HDR and LDR brachytherapy; 7.9% had interstitial brachytherapy (5.7% LDR and 1.9% HDR, 0.3% mixed). In facilities that treated >2 patients per year, 15.5% and 9.4% of brachytherapy procedures included HDR or interstitial, respectively; in facilities that treated fewer patients, 3.4% had HDR brachytherapy, and only 1.2% had interstitial brachytherapy. Patients treated with LDR intracavitary radiotherapy had one (23.5%), two (74.1%), or three (2.4%) implants. For patients treated with curative intent who completed radiation therapy with LDR intracavitary radiation therapy without hysterectomy, the median brachytherapy dose to Point A was 40.3 Gy, and the median total dose to Point A was 82.9 Gy. Patients were treated with HDR intracavitary radiation therapy using a variety of treatment schedules using 1-2 fractions (7.5%), 3-4 fractions (17.4%), 5-6 fractions (38.5%), 7-9 fractions (33.5%), or 12 fractions (3%). Fraction sizes were <500 cGy (29.5%), 500-<600 (25.2%), 600 (28.1%), >600 (8%), or unknown (9.2%). For patients treated with HDR, the median total dose to Point A (corrected for fraction size using a alpha/beta = 10) was 85.8 Gy (range: 56.2-116.1 Gy). At institutions treating <500 new patients per year, the percentage of patients receiving a brachytherapy dose <40 Gy was significantly higher than at institutions treating > or =500 new patients per year (p < 0.0001). For LDR intracavitary radiation therapy, 5.8% had neither bladder nor rectal doses recorded for any of their implants, whereas in HDR intracavitary radiation therapy, 73.4% had neither bladder nor rectal doses recorded for any of their implants. The median total duration of radiation therapy was identical for patients who had HDR or LDR intracavitary radiation therapy (57 days). For LDR at institutions treating <500 new patients per year, the percentage of patients with treatment duration >56 days was significantly greater than at institutions > or =500 new patients per year (p = 0.002). Of the patients who had LDR intracavitary radiation therapy implants, 65% were treated using tandem and shielded Fletcher-Suit-Delclos colpostats; other patients had mini ovoids (10.9%), cylinders (3.9%), Henschke (3.7%), or other/mixed applicators (16.5%). In contrast, of patients treated with HDR intracavitary radiation therapy, 68.7% had tandem and rings, 18.2% Fletcher-Suit-Delclos ovoids, 7.5% mini ovoids, 2.3% cylinders, and 3.2% other or mixed applicators. Conclusions: The median duration of treatment and median Point A dose were very similar for patients treated with HDR or LDR. Patients with HDR were treated using a variety of treatment schedules. Different applicator types were favored for LDR vs. HDR. Of patients treated with HDR, 73.4% had no brachytherapy bladder or rectal doses recorded, suggesting that full dosimetric calculations were performed only for the first fraction in many institutions. Facility size significantly impacted on referral to another institution for brachytherapy, brachytherapy dose, and treatment duration.     

宫颈癌高低剂量率^137铯腔内后装放疗的比较

回顾性分析高剂量率（HDR）和低剂量率（LDR）腔内后装治疗宫颈癌。LDR组采用我院1979年6月～1984年12月137铯腔内后装放射治疗子宫颈癌862例。HDR组采用我院1986年12月至1987年7月137铯腔内后装治疗宫颈癌135例。结果：5年存活率HDR组低於LDR组；Ⅱ级放射性直肠炎HDR组为13．0％，低於LDR组22．6％（P＜0．01）。两组Ⅱ、Ⅲ期患者中无癌存活5年以上者宫旁A点吸收剂量比值（HDR／LDR）为0．53～0．54。结论：此剂量率转换系数对指导临床实践有参考价值。     

The importance of brachytherapy technique in the management of primary carcinoma of the vagina.

This retrospective analysis of 49 cases of primary carcinoma of the vagina treated with radiation therapy alone from 1970-1988 examines the results of treatment with an emphasis on the importance of brachytherapy technique. Thirty-six patients were treated with combined external beam radiation and brachytherapy, 11 patients were treated with external beam alone, and two patients were treated with brachytherapy alone. Brachytherapy techniques used included intracavitary implants, temporary Ir-192 interstitial implants, and permanent I-125 interstitial implants. Intracavitary therapy included the use of a fractionated high dose rate intravaginal cylinder, tandem and ovoids, and a low dose rate intravaginal cylinder. The 5-year actuarial survival was 44% for Stage I (six patients), 48% for Stage II (27 patients), 40% for Stage III (10 patients), and 0% for Stage IVa and IVb (six patients). There was a significant increase in the 5-year actuarial survival for those patients who had brachytherapy as part of their treatment compared to those patients treated with external beam alone (50% vs. 9%) (p < .001). For Stages II and III, there was a trend toward improved actuarial and crude disease free survival with the use of a temporary Ir-192 interstitial implant as part of the treatment compared to the use of intracavitary brachytherapy as part of the treatment (80% vs. 45%) (p = 0.25) and (75% vs. 44%) (p = 0.08), respectively. Brachytherapy plays an important role in the management of primary vaginal cancer. A temporary interstitial implant should be used over an intracavitary form of therapy for more invasive disease.     

Present and future in brachytherapy--from the discovery of radium to the 21st century]

Brachytherapy can deliver high doses of radiation to a tumor with only low doses to the normal tissue. Brachytherapy can be classified as intracavitary, intraluminar and interstitial radiotherapy. It can be also divided into three groups according to dose rate: low (LDR), medium (MDR) and high (HDR) dose rates. In recent years, HDR remotely controlled afterloading systems are widespread in Japan. HDR brachytherapy has solved the problem of radiation exposure for medical staff, and patients need not be isolated in highly sealed rooms. Local control rates of T1 and T2 tongue cancer treated with LDR interstitial radiation using 226Ra and 192Ir were 80% and 67%. A phase III trial of HDR versus LDR interstitial brachytherapy for early tongue cancer revealed the same local control rates between the two groups. For uterine cervix cancer, the cause-specific survival rates of patients treated with HDR intracavitary brachytherapy were almost the same as those treated with LDR. HDR brachytherapy can be applied against recurrent tumors. Almost half of recurrent tumors can be controlled with HDR treatment. Brachytherapy is widely used for prostate cancer in the USA. LDR brachytherapy using 125I seeds is used for prostate cancer. In Japan, 125I seeds can not be used because of the regulation of radioisotopes, so we treat prostate cancer patients with HDR brachytherapy. The two-year biochemical NED rate is 83%. Brachytherapy has a long history of nearly 100 years. In recent years, the development of an HDR remotely controlled afterloading system and treatment planning system allows us to make a precise treatment plan and a uniform dose distribution. In the next century, HDR-brachytherapy will continue to play an important role in the field of radiotherapy.     

Vaginal recurrences of endometrial carcinoma: the prognostic value of staging by a primary vaginal carcinoma system

Fifty-five of 1716 women with endometrial carcinoma seen consecutively at three institutions prior to 1986 were found to have an isolated post-hysterectomy vaginal recurrence. Their therapy included external radiation therapy (RT) and brachytherapy for 26 women, external RT alone for 17, brachytherapy only for 4, and no RT for 8. Combined external RT/brachytherapy doses ranged from 2000 to 10,000 cGy with a median of 6000 cGy. The 3- and 5-year actuarial survival rates are 48% and 31% for the entire group, and the 3- and 5-year pelvic control rates are 52% and 42%. The 5-year survival and pelvic control rates for those who received greater than or equal to 6000 cGy in total RT dose are 47% and 68%, compared with 12% and 10% for those receiving less than 6000 cGy (p = 0.002 and p = 0.004). For patients receiving their second RT course, the 5-year survival rate is 16%, compared with 48% for those not previously irradiated. The Perez modification of the International Federation of Gynecology and Obstetrics (FIGO) staging system for primary vaginal carcinoma was applied to each recurrence. There were 15 Stage I cases (vaginal mucosa), 32 Stage II cases divided between 15 Stage IIA (subvaginal infiltration) and 17 in Stage IIB (parametrial infiltration), and 8 Stage III cases (pelvic wall involvement). The 3-year actuarial survival and pelvic control rates using this staging system are: Stage I: 85%/100%; Stage II: 41%/43%, Stage IIA: 59%/53%, Stage IIB: 26%/35%; Stage III: 13%/0%. These outcome endpoints are significantly better for Stage I than Stage II patients (p = 0.01 & 0.0004) and for Stages I and IIA compared to Stages IIB and III (p = 0.0005 & 0.002). The pre-treatment variables of age, interval since hysterectomy, initial stage, and location did not predict for survival, but a higher rate of pelvic control was observed for apical than for suburethral recurrences (56% vs. 20%). Grade III histology was highly correlated with poor survival (p = 0.0006). This vaginal carcinoma staging system appears to have value in predicting treatment outcome for patients with post-hysterectomy vaginal recurrences.