Clinical Investigation
Five Years' Experience Treating Locally Advanced Cervical Cancer With Concurrent Chemoradiotherapy and High-Dose-Rate Brachytherapy: Results From a Single Institution

https://doi.org/10.1016/j.ijrobp.2008.06.1920Get rights and content

Purpose

To assess the clinical outcomes after concurrent cisplatin chemotherapy and radiotherapy (RT) followed by high-dose-rate brachytherapy for locally advanced carcinoma of the cervix and perform a multivariate analysis of the prognostic factors.

Methods and Materials

The outcomes were analyzed for all women treated between 1999 and 2004 with concurrent cisplatin chemotherapy and RT followed by high-dose-rate brachytherapy. Kaplan-Meier analysis was used for overall survival (OS), local control (LC), and distant control (DC). The Cox proportional hazards model was used to perform multivariate analysis of the prognostic variables.

Results

The standard regimen comprised whole pelvic external RT 45 Gy in 25 fractions with concurrent weekly cisplatin 40 mg/m2, followed by four high-dose-rate brachytherapy insertions of 6 Gy. Patients with radiologically enlarged para-aortic lymph nodes underwent extended-field RT. Of 92 patients, the OS rate was 72% at 2 years and 55% at 5 years. The LC rate was 76% at 2 years and 67% at 5 years. The DC rate was 68% at 2 years and 48% at 5 years. The most important prognostic factor for OS, LC, and DC was the pretreatment hemoglobin. For OS, the tumor size and the presence of enlarged lymph nodes were also important. For LC, the number of brachytherapy insertions was important; and for DC, the number of chemotherapy treatments was important. Of the patients, 4% experienced late Grade 3 or 4 toxicity.

Conclusion

The results of our study have shown that the regimen is effective, with acceptable long-term side effects. In this cohort, the most important prognostic factor was the pretreatment hemoglobin level, a disease-related factor. However, more effective systemic treatments are needed.

Introduction

Cervical cancer is the second most common cause of female cancer death worldwide. The incidence is greatest in developing countries, and the peak incidence is in the 40–45-year age group. Although in the United Kingdom, the incidence has decreased in recent years because of the success of the national screening program to 9/100,000 women, the European Age Standardised Rate 1, 2, 3, 4, cervical cancer is still a significant cause of morbidity and mortality. Until 1999, the main curative treatment option for patients with bulky tumors was radical radiotherapy (RT) using external beam RT and brachytherapy. However, after the publication of five randomized trials 5, 6, 7, 8, 9, a consensus of expert opinion (10), and two meta-analyses 11, 12, the standard treatment has become concurrent cisplatin-based chemotherapy and radical RT.

Worldwide, most experience in brachytherapy for carcinoma of the cervix has been with low-dose-rate (LDR) treatment. Radiation protection issues and machine availability have led to the more widespread use of high-dose-rate (HDR) brachytherapy, but few randomized trials have examined its use. Those that have been published 13, 14, 15, 16, 17, 18, 19 have been examined by the National Institute for Clinical Excellence (NICE) (20), which concluded that the use of HDR brachytherapy for cervical cancer gave overall survival (OS) rates similar to those with medium-dose-rate or LDR brachytherapy when used in combination with external beam RT.

With regard to the use of concurrent chemoradiotherapy and HDR brachytherapy, very few published series have examined its benefits and toxicities, and no standard treatment regimen exists. The present report considered 5 years' experience at the Velindre Cancer Centre, Cardiff, United Kingdom using radical RT and concurrent chemotherapy with cisplatin followed by HDR brachytherapy for primary treatment of Stage IB–IVA cervical cancer, including those with radiologically enlarged pelvic or para-aortic lymph nodes.

Section snippets

Data collection

The Velindre Cancer Centre is a tertiary referral center specializing in nonsurgical oncology treatment. Most referrals are from within the South East Wales Cancer Network. All women treated for cervical cancer at the Velindre Cancer Centre between June 1999 and May 2004 were identified. They were grouped according to treatment, and all those who were treated with primary chemoradiotherapy with cisplatin were included in this data set. For each patient, the case notes were evaluated to collect

Radiotherapy compliance

Of the 92 women, 91 (98.9%) completed the planned external beam RT; 84 (91.3%) completed all the planned RT (external beam RT and brachytherapy). Of the 8 women who did not, 1 patient had missed an external beam fraction receiving only 43.2 Gy but still had all four brachytherapy insertions (EQD2, 74.5 Gy), and 7 had completed the external beam RT but had fewer than four brachytherapy insertions. Of these 7 patients, 4 had three of four brachytherapy insertions (EQD2, 68.25 Gy; 1 patient was

Discussion

The series we have presented has demonstrated that concurrent chemoradiotherapy with cisplatin and HDR brachytherapy is safe and effective. One of the strengths of this study was that it included all patients treated with this regimen; therefore, it represents the results of treatment in the general population. A limitation of the study, because it was retrospective, was that late Grade 1 or 2 toxicity might have been underestimated.

Conclusion

The schedule we have presented is a safe primary treatment for cancer of the uterine cervix in our population. To our knowledge, this regimen has not been previously reported. The pretreatment hemoglobin level, tumor size, and the presence of lymphadenopathy were all independent prognostic factors for OS in our multivariate analysis. The number of brachytherapy insertions was prognostic for LC. The number of chemotherapy treatments was prognostic for metastatic control, supporting the possible

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