Clinical investigation: Brachytherapy
Treatment of recurrent gynecologic malignancies with iodine-125 permanent interstitial irradiation

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Abstract

Purpose: To analyze the outcome of permanent 125I interstitial radiotherapy for unresectable retroperitoneal recurrences of gynecologic malignancies.

Methods and Materials: A retrospective review of 20 patients treated between 1979 and 1993 was performed to evaluate survival and morbidity associated with the interstitial 125I technique.

Results: Nineteen tumors were located on the lateral pelvic wall and one in the para-aortic region. Eight patients, not previously irradiated, received external beam radiotherapy (EBRT) along with 125I interstitial implants placed at the time of celiotomy. Nineteen (95%) are dead of disease at 1–69 months of follow-up. The median survival was 7.7 months for patients treated with 125I alone and 25.4 months for those treated with both 125I and EBRT. One patient is alive without evidence of disease 69 months after 125I implantation. Fistulas, bowel obstructions, and fatal complications occurred only among patients previously irradiated.

Conclusions: When used in a previously irradiated field, 125I interstitial radiotherapy has major morbidity and is unlikely to be associated with cure or long-term survival. In radiotherapy-naive patients with unresectable isolated recurrent gynecologic malignancies, 125I implants and EBRT are feasible and occasionally may contribute to long-term disease-free survival.

Introduction

While many gynecologic neoplasms have the potential for pelvic sidewall recurrence, locally advanced cervical cancer is notorious for this. According to the Annual Report on the Results and Treatment in Gynecological Cancer prepared by the International Federation of Gynecology and Obstetrics (FIGO), by 1988, 85% of cervical cancer patients were receiving definitive or adjuvant radiotherapy as part of their treatment program (1). Forthwith, the vast majority of patients who relapse constitute radiation failures. Ultraradical surgery may be employed to rescue women with central pelvic failures not associated with concomitant distant metastases. Indeed, following Alexander Brunschwig’s original report in 1948 (2), several centers have reported 5-year survival rates following pelvic exenteration that have ranged from 20% to 50% (3). For example, Felix Noah Rutledge and colleagues reported a 48.3% 5-year survival rate in a select group of patients with recurrent cervical cancer treated by pelvic exenteration at the M.D. Anderson Hospital and Tumor Institute in Houston (4). The emergence of this specific subpopulation among women with recurrent cervical cancer has enabled us to define a potentially curable high-risk cohort. Of course, careful patient selection is predicated on the constellation of medical, psychological, and oncologic criteria.

Women with retroperitoneal recurrences, specifically those infiltrating the pelvic sidewall or periaortic regions, are a therapeutic challenge. It is mandatory that this group also be studied, as sidewall recurrences after irradiation manifest two to three times more frequently than central failures. Historically, most investigators have considered such recurrences biologically distinct from those occurring in the central pelvis due to the observation that sidewall recurrences are derived predominantly from primary lesions with lymph node metastases, which, by consequence, may indicate systemic dissemination. Furthermore, lymph node negative primary tumors had been noted to recur more frequently in the central pelvis.

External irradiation has been unsuccessful in sterilizing bulky sidewall disease and cure rates of almost zero had been previously documented among patients with sidewall recurrences subjected to extirpative surgery (5). For these reasons, locoregional therapy for patients with retroperitoneal recurrences has not been available for tumor control and women with infiltrating pelvic sidewall lesions have been treated with palliative systemic or investigational therapy, irrespective of the presence or absence of demonstrable distant disease. This also holds for patients with perioaortic recurrence.

Over the preceding two decades, innovative strategies of administering interstitial irradiation have been devised, including transperineal interstitial thermoradiation and the combined operative and radiotherapeutic treatment (CORT). Because the distorted geometry and inaccessibility of unresectable high pelvic sidewall and periaortic recurrences can make transperineal and transabdominal interstitial brachytherapy technically impractical in many cases, a third interstitial technique involving permanent interstitial seed implantation has evolved to address the clinical problem of retroperitoneal recurrences in gynecologic cancer. The presence of several long-term cures among recurring patients salvaged with one of these new interstitial irradiation modalities has prompted many to reconsider the prevailing hypothesis that so-called “isolated” sidewall recurrences by definition must reflect subclinical distant disease (3).

We therefore submit that effective locoregional therapy may exist for some women with retroperitoneal recurrences. The purpose of this study is to review and update our experience with permanent 125I seed interstitial endocurietherapy among patients with isolated, unresectable infiltrating disease of the pelvic sidewall or periaortic region following primary therapy with irradiation or surgery.

Section snippets

Methods and materials

Retrospective review of clinical data were approved by the Institutional Review Boards at the University of California, Irvine-Medical Center and at Long Beach Memorial Medical Center, in accordance with assurances filed with and approved by the U.S. Department of Health and Human Services. Tumor registry abstracts and medical records at both institutions were reviewed to identify those patients treated with 125I seed permanent interstitial brachytherapy from January 1979 through December 1993,

Results

Between 1979 and 1993, 41 patients with recurrent gynecologic malignancies involving the pelvic sidewall (n = 36) or the periaortic region (n = 5) were evaluated for open interstitial permanent seed brachytherapy. Of these, 17 were excluded secondary to the presence of concomitant distant metastases, 3 patients refused to undergo laparotomy, and one was in such poor health that surgical intervention was contraindicated. Thus, the study population consisted of 19 patients with recurrent squamous

Discussion

The overall incidence of recurrent cancer from most sites is 50%, of which 20% to 30% are localized without evidence of dissemination 14, 15. At least 20% of female genital tract tumors treated for cure in North America and in Europe will relapse in the pelvis without detectable distant metastases (16). Webb, Munnell, and Figge have independently examined the critical points of failure in the treatment of gynecologic cancer 17, 18, 19, and concluded that the majority of localized pelvic

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