Clinical investigation
Cervix
Computed Tomography-Based High-Dose-Rate Intracavitary Brachytherapy for Uterine Cervical Cancer: Preliminary Demonstration of Correlation Between Dose–Volume Parameters and Rectal Mucosal Changes Observed by Flexible Sigmoidoscopy

Presented in part at the 48th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), November 5–9, 2006, Philadelphia, PA.
https://doi.org/10.1016/j.ijrobp.2007.02.009Get rights and content

Purpose: To compare the dose–volume histogram (DVH) parameters obtained by three-dimensional gynecologic brachytherapy planning with the rectosigmoid mucosal changes observed by flexible sigmoidoscopy.

Methods and Materials: Between January 2004 and July 2005, 71 patients with International Federation of Gynecology and Obstetrics Stage IB–IIIB uterine cervical cancer underwent computed tomography-based high-dose-rate intracavitary brachytherapy. The total dose (external beam radiotherapy [RT] plus intracavitary brachytherapy) to the International Commission of Radiation Units and Measurements rectal point (ICRURP) and DVH parameters for rectosigmoid colon were calculated using the equivalent dose in 2-Gy fractions (α/β = 3 Gy). Sigmoidoscopy was performed every 6 months after RT, with the 6-scale scoring system used to determine mucosal changes.

Results: The mean values of the DVH parameters and ICRURP were significantly greater in patients with a score of ≥2 than in those with a score <2 at 12 months after RT (ICRURP, 71 Gyα/β3 vs. 66 Gyα/β3, p = 0.02; D0.1cc, 93 Gyα/β3 vs. 85 Gyα/β3, p = 0.04; D1cc, 80 Gyα/β3 vs. 73 Gyα/β3, p = 0.02; D2cc, 75 Gyα/β3 vs. 69 Gyα/β3, p = 0.02). The probability of a score of ≥2 showed a significant relationship with the DVH parameters and ICRURP (ICRURP, p = 0.03; D0.1cc, p = 0.05; D1cc, p = 0.02; D2cc, p = 0.02).

Conclusion: Our preliminary data have shown that DVH values of the rectosigmoid colon obtained by computed tomography-based three-dimensional brachytherapy planning are reliable and predictive of score ≥2 rectosigmoid mucosal changes.

Introduction

Intracavitary brachytherapy (ICBT) is an essential component of radiotherapy (RT) for patients with uterine cervical cancer because it delivers a high dose to the primary cervical lesion and adjacent soft tissues, resulting in increased local control and survival (1). Traditionally, Points A and B, which represent the dose in the paracervical triangle and the pelvic wall, respectively, have been used to prescribe the radiation dose and to report the treatment results according to two-dimensional brachytherapy planning (2). In addition, the rectal and bladder points have been defined by the International Commission of Radiation Units and Measurements (ICRU) to represent the dose to the organs at risk (OARs) and estimate the risk of late complications. These points can be reproducibly calculated using two-dimensional orthogonal radiographs (3, 4, 5) and, hence, have been used to report and compare treatment results from different institutions. However, these points do not take the exact tumor and normal tissue anatomy into account and also could be more subject to day-to-day variation caused by differing extents of bladder and bowel filling. The use of highly sophisticated imaging modalities, such as high-speed computed tomography (CT) and magnetic resonance imaging (MRI), has enabled more detailed anatomic information to be brought into clinical RT practice. Recently, three-dimensional (3D) planning has also been introduced into gynecologic brachytherapy planning (6, 7, 8, 9), providing accurate dose–volume histogram (DVH) parameters for the gross tumor volume, clinical target volume (CTV) and OARs.

Rectal complications are one of the major concerning morbidities that include urinary complications, small bowel complications, and large bowel complications in patients treated with a combination of external beam RT (EBRT) and ICBT for uterine cervical cancer. Because small-volume irradiation exceeding the tolerance dose could result in severe late complications to the rectum, the importance of the volume effect in this organ has been less emphasized. More information about the dose–volume effect on the rectum has been derived from experience with conformal therapy for prostate cancer (10, 11). Severe late damaging effects to the rectum, including strictures, ulcerations, and necrosis, are associated with changes in the vascular structures of the rectal submucosa. Irradiation of the rectum commonly causes congestion and edematous mucosal changes initially and, in later stages, results in microscopic changes to the submucosal layer, including fibroblast proliferation, thickening of the small arterial vessel walls, and formation of telangiectatic vessels (12). Because the latter has been found to further hamper local blood flow and to be responsible for late fibrosis and necrosis, we used the telangiectatic change of the mucosa as the most important parameter in sigmoidoscopic scoring in our previous short-term analysis (13).

In July 2003, we began a prospective clinical study to examine the relationship between the DVH parameters obtained from 3D brachytherapy planning and complications in the rectosigmoid colon. Apart from the symptoms of rectal bleeding, we used serial flexible sigmoidoscopy to assay the changes in the mucosa of the rectum and sigmoid colon that might precede the development of clinical signs and symptoms. This report provides the results of the preliminary analysis of DVH data for the first 71 patients who were followed by regular flexible sigmoidoscopy for 1 year after treatment.

Section snippets

Patient population

The protocol for this study was approved by the institutional review board of the National Cancer Center, Republic of Korea, and all patients provided written informed consent. A total of 142 patients were registered at the analysis, and the data from the first 71 patients who were followed with at least two consecutive sigmoidoscopic examinations after treatment completion were included in this report. The eligibility criteria included a histologically confirmed diagnosis of cervical cancer,

Patient characteristics

Between January 2004 and July 2005, we enrolled 71 patients with uterine cervical cancer. The median patient age at the initial presentation was 56 years (range, 23–77). All the patients had International Federation of Gynecology and Obstetrics (FIGO) Stage IB–IIIB disease. Of the 71 patients, 62 (87%) had squamous cell carcinoma, 4 (6%) had adenocarcinoma, and 5 (7%) had an unspecified carcinoma. Of the 71 patients, 17 (24%) had Stage IB, 13 (18%) had Stage IIA, 32 (45%) had Stage IIB, 2 (3%)

Discussion

Rectal complications are one of the major concerning morbidities in patients with cervical cancer undergoing brachytherapy. Before DVHs were available, the ICRURPs, maximal rectal points, and/or additional parameters, such as the ICRURP dose/Point A ratio, were used to determine the radiation dose levels associated with severe rectal complications (19, 20, 21, 22, 23, 24, 25, 26, 27, 28). We have previously showed that a total dose greater than the biologically effective dose of 125 Gy3 at the

Conclusion

Our preliminary data have shown that several DVH parameters (D0.1cc, D1cc, and D2cc) obtained from 3D CT-based treatment planning are significantly associated with the endoscopic scoring of mucosal changes in the rectosigmoid colon. As a follow-up to this work, our future studies will include the correlation of these DVH parameters with the clinical incidence of late complications and tumor control rates, as well as with long-term sigmoidoscopic follow-up data. These studies will aid in

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    Conflict of interest: none.

    This study was implemented under the National Cancer Center Clinical Trial NCCCTS 04-099 and partly supported by National Cancer Center Grant 0610510.

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