Dose optimization of fractionated external radiation and high-dose-rate intracavitary brachytherapy for FIGO stage IB uterine cervical carcinoma

Abstract

$\text{Purpose}$: To determine the optimal dose combination scheme of external beam radiotherapy (EBRT) and high-dose-rate (HDR) intracavitary radiation (ICR) for maximizing tumor control while conferring an acceptable late complication rate in the treatment of Stage IB uterine cervical cancer.

$\text{Methods and Materials}$: We retrospectively analyzed 162 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IB squamous cell carcinoma of the uterine cervix who received definitive RT between May 1979 and December 1990. Before HDR-ICR, all patients received EBRT to a total dose of 40–46 Gy (median 45), administered during 4–5 weeks to the whole pelvis. HDR-ICR was given 3 times weeks to a total dose of 24–51 Gy (median 39) at point A, using a dose of 3 Gy/fraction. Central shielding from EBRT was begun after the delivery using 20–45 Gy (median 40) of the external dose. The total dose to point A, calculated by adding the EBRT biologically effective dose (BED) and the ICR BED to point A, was 74.1–118.1 Gy (mean 95.2). The rectal point dose was calculated at the anterior rectal wall at the level of the cervical os. The local control rate, survival rate, and late complication rate were analyzed according to the irradiation dose and BED.

$\text{Results}$: The initial complete response rate was 99.4%. The overall 5-year survival rate and 5-year disease-free survival rate was 91.1% and 90.9%, respectively. The local failure rate was 4.9%, and the distant failure rate was 4.3%. Late complications were mild and occurred in 23.5% of patients, with 18.5% presenting with rectal complications and 4.9% with bladder complications. The mean rectal BED (the sum of the external midline BED and the ICR rectal point BED) was lower in the patients without rectal complications than in those with rectal complications (125.6 Gy vs. 142.7 Gy, p = 0.3210). The late rectal complication rate increased when the sum of the external midline BED and the rectal BED by ICR was ≥131 Gy (p = 0.1962). However, 5-year survival rates did not increase with the external midline BED (p = 0.4093). The late rectal complication rate also increased, without a change in the survival rate, when the sum of the external midline BED and the ICR point A BED was >90 Gy.

$\text{Conclusion}$: In treating Stage IB carcinoma of the uterine cervix with HDR-ICR, using fractions of 3 Gy, it is crucial to keep the point A BED at ≤90 Gy to minimize late rectal complications without compromising the survival rate. To achieve this goal, appropriate central shielding from EBRT is needed.

Introduction

A review of the literature suggests that approximately 80–90% of patients who have Stage IB carcinoma of the uterine cervix is defined in the International Federation of Gynecology and Obstetrics (FIGO) can be cured using just definitive radiotherapy (RT) that consists of external beam RT (EBRT) combined with intracavitary radiation (ICR) 1, 2, 3, 4, 5, 6, 7. However, no study has established the optimal dose combination scheme and radiation doses to minimize complications due to the radiation without compromising the survival rate. Many radiation oncologists have described appropriate dose combinations for EBRT and ICR on the basis of rates of cure and late complications. Generally, Grade II-III complications have been reported to occur in about 5% of patients with early-stage cervical cancer: but the incidence of complications is higher if the dose to point A is >80 Gy 3, 8, 9, 10, 11. These findings have mostly been obtained in studies using low-dose-rate (LDR) ICR. The appropriate combination of radiation types and doses has also not been defined for high-dose-rate (HDR) ICR 3, 9, 12, 13, 14, although the use of HDR brachytherapy is now expanding in the clinic 15, 16.

Since the introduction of HDR-ICR at our institution in 1979, we have published one report comparing our early experience using HDR-ICR with that using LDR-ICR in Korea (12). We reported that because of the physical and radiobiologic uncertainty of HDR-ICR, during the years 1979–1983, central shielding for EBRT was done from the beginning or after the delivery of 20 Gy of EBRT for patients with FIGO Stage I cervical cancer in an attempt to reduce radiation-induced complications. Because it had survival and complication rates comparable to those of LDR-ICR, this HDR-ICR protocol could be considered a safe RT method capable of being used on an outpatient basis. However, the survival rate of 80% for FIGO Stage IB patients was unsatisfactory (although it was not statistically significantly different from that for LDR-ICR patients). These results prompted us to change our HDR-ICR treatment protocol for early-stage carcinoma of the uterine cervix in 1984. Despite using the same fractionation scheme of HDR-ICR, no central shielding was done during EBRT to escalate the central dose, resulting in considerably increased complication rates (unpublished data); the protocol was thus abandoned in 1988. Since then, central shielding for EBRT has been initiated after delivery of an external dose of 30–36 Gy.

These changes in the protocol have allowed us to collect a large cohort of patients with FIGO Stage I uterine cervical cancer who were treated with a wide range of central doses during the protocols’ lifetimes. The aim of the present study was to determine the dose combination scheme of EBRT and HDR-ICR that maximizes tumor control and provides an acceptable rate of late complications in the treatment of Stage IB uterine cervical cancer.