Distant metastasis in patients with cervical cancer after primary radiotherapy with or without chemotherapy and image guided adaptive brachytherapy
Introduction
Cervix cancer is one of the most common malignancies in women worldwide and still remains a prominent cause of female cancer death [1], [2]. Radiotherapy has been the mainstay of treatment for locally advanced cervix cancer for decades. Since the late nineties chemotherapy is added to standard radiotherapy as this addition improves overall and disease free survival by about 6% at 10 years [3]. Besides improving the effectiveness of radiotherapy in terms of improvement of local tumour control, the addition of chemotherapy also decreases the rate of distant metastases, but to a lesser extent [3], [4]. In spite of the clear benefits of adding chemotherapy to radiotherapy for cervix cancer patients, many questions still remain regarding the optimal agent and timing, as well as the added benefit for the higher stages [3], [4].
More recently, technological advances in radiotherapy have led to significant improvements in local tumour control. With image guided adaptive brachytherapy (IGABT) a local control rate of > 90–95% appears to be achievable for all tumour stages. These promising findings in several single institution series are currently the subject of a multicenter verification in the EMBRACE study (European study on MRI guided BRAchytherapy in locally advanced CErvix cancer) [5], [6], [7], [8], [9], [10], [11]. However, it still needs to be clarified to which extent this improvement in local control translates into an improvement in overall or distant metastases-free survival [3], [5], [12], [13].
Hence, in the setting of an excellent local control resulting from IGABT for locally advanced cervical cancer, distant failure emerges as the predominant type of failure for these patients.
We performed a retrospective analysis of patients with locally advanced cervix cancer treated with definitive radiotherapy including IGABT to (1) investigate time to occurrence of distant metastases and patterns of spread, (2) determine the impact of prognostic factors on the occurrence of distant metastases, (3) analyse the impact of chemotherapy on the occurrence of distant metastases.
Section snippets
Patients
All patients with cervix cancer FIGO Ib to IVa treated with definitive radiotherapy between January 1998 and June 2009 at the Department of Radiation Oncology of the Medical University of Vienna were included in this retrospective analysis. Patients were excluded from this analysis in case of local/regional recurrence, delivery of neoadjuvant chemotherapy or a contraindication for chemotherapy due to patient age.
Pre-treatment evaluation included patient history, complete physical and
Patient and treatment characteristics
A total number of 253 patients with primary locally advanced cervix cancer were treated with definitive radiotherapy with or without chemotherapy between January 1998 and June 2009.
Of these 253, 189 met the inclusion criteria for this analysis. The reasons for excluding the 64 patients were loco-regional failure (n = 30) or failure to achieve a complete response (n = 8), no chemotherapy administered due to age (n = 23) or neoadjuvant chemotherapy administered (n = 3). Patient- and tumour
Discussion
Chemoradiation as a standard treatment approach for patients with locally advanced cervix cancer gained widespread acceptance since several large randomised trials showed improved local control and overall survival with the addition of chemotherapy to radiotherapy [22], [23], [24], [25], [26], [27]. However, the optimal timing, dose and sequence of chemotherapy are still not fully elucidated. Concomitant chemotherapy, though administered at low dose, may also decrease the incidence of distant
Conflict of interest statement
The Department of Radiotherapy at the Medical University of Vienna receives/received financial and/or equipment support for research and educational purposes from Nucletron an Elekta company and Varian Medical Systems, Inc. The financial support by the Austrian Federal Ministry of Economy, Family, and Youth and the Austrian Foundation for Research, Technology, and Development is gratefully acknowledged.
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