Distant metastasis in patients with cervical cancer after primary radiotherapy with or without chemotherapy and image guided adaptive brachytherapy

https://doi.org/10.1016/j.ygyno.2014.02.004Get rights and content

Highlights

  • FIGO stage and lymph node status are significant predictors for distant metastasis in cervical cancer patients.

  • 5 year distant metastasis free survival of 91% and 60% in low and high risk patients

  • Significant impact of number of chemotherapy cycles on the occurrence of distant metastasis in high risk patients

Abstract

Objective

The aim of this study is to investigate patterns of distant relapse after primary radiochemotherapy in cervical cancer patients.

Methods

All patients with cervical cancer treated in curative intent with external beam radiotherapy +/− chemotherapy and image-guided adaptive brachytherapy between January 1998 and June 2009 at the Medical University of Vienna were included in this retrospective analysis. Patients with locoregional recurrences were excluded from this study. Presence, site of and time to distant metastases were recorded. For identifying prognostic factors, uni- and multivariate analyses using Cox regression analysis were performed. Based on the result from the multivariate analysis, patients were stratified into a high and a low risk group. The Kaplan–Meier method was used to estimate distant-metastasis-free-survival in the overall cohort, in the risk groups and for analysing the impact of chemotherapy within the risk groups.

Results

A total number of 189 patients were included in this study. After a median follow-up of 54 months, 49 patients developed distant metastases. Overall, distant-metastasis-free-survival 5 years after treatment was 73%. FIGO stage, lymph node status and the extent of tumour regression during treatment were significant predictors for distant metastasis. Distant-metastasis-free-survival 5 years after treatment was 91% and 60% in the low and high risk groups, respectively. The number of the cycles of chemotherapy had a significant impact on the occurrence of distant metastasis in high risk patients, but not in low risk patients.

Conclusion

Patients with high risk factors have a 40% probability of developing distant metastasis within 5 years. In these patients, decreasing the number of cycles of cisplatin may increase their probability of developing distant metastasis.

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.

References (43)

  • R. Potter et al.

    Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology

    Radiother Oncol

    (2006)
  • J.C. Dimopoulos et al.

    The Vienna applicator for combined intracavitary and interstitial brachytherapy of cervical cancer: clinical feasibility and preliminary results

    Int J Radiat Oncol Biol Phys

    (2006)
  • C. Kirisits et al.

    Dose and volume parameters for MRI-based treatment planning in intracavitary brachytherapy for cervical cancer

    Int J Radiat Oncol Biol Phys

    (2005)
  • P. Trnkova et al.

    New inverse planning technology for image-guided cervical cancer brachytherapy: description and evaluation within a clinical frame

    Radiother Oncol

    (2009)
  • J.C. Dimopoulos et al.

    Inter-observer comparison of target delineation for MRI-assisted cervical cancer brachytherapy: application of the GYN GEC-ESTRO recommendations

    Radiother Oncol

    (2009)
  • T.P. Hellebust et al.

    Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group: considerations and pitfalls in commissioning and applicator reconstruction in 3D image-based treatment planning of cervix cancer brachytherapy

    Radiother Oncol

    (2010)
  • E.K. Nugent et al.

    Chemoradiation in locally advanced cervical carcinoma: an analysis of cisplatin dosing and other clinical prognostic factors

    Gynecol Oncol

    (2010)
  • H. Fagundes et al.

    Distant metastases after irradiation alone in carcinoma of the uterine cervix

    Int J Radiat Oncol Biol Phys

    (1992)
  • H. Sakurai et al.

    Analysis of recurrence of squamous cell carcinoma of the uterine cervix after definitive radiation therapy alone: patterns of recurrence, latent periods, and prognosis

    Int J Radiat Oncol Biol Phys

    (2001)
  • M.P. Schmid et al.

    Local recurrences in cervical cancer patients in the setting of image-guided brachytherapy: a comparison of spatial dose distribution within a matched-pair analysis

    Radiother Oncol

    (2011)
  • S. Polterauer et al.

    External validation of a nomogram predicting overall survival of patients diagnosed with endometrial cancer

    Gynecol Oncol

    (2012)
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