Clinical investigation
Preliminary analysis of chronic gastrointestinal toxicity in gynecology patients treated with intensity-modulated whole pelvic radiation therapy

Presented at the 44th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, New Orleans, LA, October 6–10, 2002.
https://doi.org/10.1016/S0360-3016(03)00325-0Get rights and content

Abstract

Purpose

To provide a preliminary analysis of chronic gastrointestinal (GI) toxicity in gynecology patients treated with intensity-modulated whole pelvic radiation therapy (IM-WPRT).

Methods and materials

Between February 2000 and August 2001, 36 gynecology patients received IM-WPRT. All patients underwent a contrast-enhanced computed tomography scan, and a clinical target volume (CTV) was contoured consisting of the upper vagina, parametria, uterus (if present), and presacral and pelvic lymph node regions. The CTV was expanded by 1 cm to create a planning target volume (PTV). Seven or 9-field IM-WPRT plans were generated. IM-WPRT plans were highly conformal, providing excellent coverage of the PTV and considerable sparing of normal tissues, including the small bowel and rectum. Chronic GI toxicity was scored: 0 (no symptoms), 1 (mild symptoms, no medications required), 2 (moderate symptoms, medications required), and 3 (severe symptoms, hospitalization, surgery required). Chronic GI toxicity in 30 gynecology patients treated with conventional WPRT patients before the implementation of IM-WPRT was also evaluated. Median follow-up in the IM-WPRT and WPRT groups were 19.6 and 30.2 months, respectively.

Results

The IM-WPRT and WPRT groups were well balanced in terms of most patient and treatment factors, including age, site, stage, chemotherapy, WPRT dose, and brachytherapy, except for a higher frequency of surgery (75 vs. 54%, p = 0.02) in the IM-WPRT group. Overall, IM-WPRT patients had a lower rate of chronic GI toxicity (11.1 vs. 50.0%, p = 0.001) than WPRT patients. The percentage of IM-WPRT patients with Grade 1, 2, and 3 toxicity were 8.3%, 2.8%, and 0%, respectively. Corresponding percentages in the WPRT group were 30.0%, 16.7%, and 3.3%, respectively. The only other factor correlated with chronic GI toxicity was age (p = 0.02). On multivariate (logistic regression) analysis controlling for age and other clinical factors, IM-WPRT retained its statistical significance (p = 0.01; odds ratio 0.16; 95% confidence interval 0.04, 0.67)

Conclusions

Our results suggest that IM-WPRT is associated with less chronic GI toxicity than conventional WPRT in patients with gynecologic malignancies. However, longer follow-up and more patients are clearly needed to ascertain whether the benefits of IM-WPRT treatment seen here translate into true long-term reductions in chronic GI toxicity.

Introduction

Radiation therapy (RT) is commonly used in the treatment of gynecologic tumors, notably cervical and endometrial cancer. Whereas select patients receive intracavitary brachytherapy (ICB) alone 1, 2, most receive whole pelvic RT (WPRT) alone 3, 4 or combined with ICB 5, 6. WPRT is used to treat the primary tumor (or tumor bed), parametrial tissues, and regional (pelvic) lymph nodes.

Unlike ICB, WPRT results in the irradiation of large volumes of the small bowel and rectum, commonly leading to gastrointestinal (GI) toxicity in these patients 7, 8. Acute GI symptoms typically involve varying degrees of diarrhea, cramping, and abdominal discomfort. Chronic (late) toxicity may arise months to years after WPRT. Although severe chronic toxicities (proctitis, obstruction, fistulas) are uncommon, many women treated with WPRT, nonetheless, suffer from a variety of chronic problems including intermittent diarrhea, intolerance to certain foods, and malabsorption of vitamins, lactose, and bile acids (9).

In an effort to reduce the volume of small bowel and rectum irradiated (and thus the risk of GI sequelae) in gynecology patients, we began exploring the use of intensity-modulated WPRT (IM-WPRT) in our clinic. Unlike conventional RT, intensity-modulated radiotherapy (IMRT) utilizes beams of varying intensity that conform the high dose region to the shape of the target tissues in three dimensions, thereby minimizing the dose to the surrounding organs. We 10, 11 and others 12, 13, 14, 15 have shown that IMRT planning significantly reduces the volume of both small bowel and rectum in gynecology patients undergoing WPRT. Moreover, in a series of reports 16, 17, we have noted that gynecology patients treated with IM-WPRT experience less acute GI toxicity than those treated with conventional techniques.

The question remains, however, whether IM-WPRT treatment reduces the incidence and severity of chronic GI toxicity in these patients. We began treating gynecology patients with IM-WPRT in February 2000. At present, a number of women have completed therapy and have been followed for over 1 year. The purpose of this report is to provide a preliminary analysis of chronic GI sequelae in these patients.

Section snippets

Methods and materials

Between February 2000 and August 2001, 37 women with gynecologic malignancies underwent IM-WPRT in the Department of Radiation and Cellular Oncology at the University of Chicago. One patient was excluded from our analysis due to the development of a symptomatic locoregional recurrence, leaving 36 evaluable patients for analysis of GI toxicity. The characteristics of these patients are shown in Table 1. Most (56%) had cervical cancer, predominantly Stages I–II. Whereas 9 underwent RT alone, 27

Results

Overall, 4 IM-WPRT patients (11%) developed chronic GI toxicity: 3 Grade 1 and 1 Grade 2. All four complained of diarrhea after the ingestion of certain foods, predominantly raw fruit and/or vegetables. The sole Grade 2 patient required infrequent antidiarrheal medications due to food intolerances. No IM-WPRT patient developed a Grade 3 chronic GI toxicity. Thirty-two IM-WPRT patients (89%) stated that they had no GI symptoms and were able to eat all types of food.

Fifteen WPRT patients (50%)

Discussion

The application of IMRT in gynecologic oncology patients has been receiving increasing attention in the literature 10, 11, 12, 13, 14, 15, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27. By far, the majority of these reports have focused on the use of IM-WPRT 10, 11, 12, 13, 16, 17, 19, 20, 21, 23, 26, 27. In our initial comparison study (10), we found that the small bowel volume treated to the prescription dose was reduced by a factor of 2 using IM-WPRT. In addition, the volume of rectum and

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Supported by a grant from the Illinois Department of Public Health.

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