Clinical Oncology
Volume 22, Issue 7 , Pages 602-604, September 2010

Brachytherapy for Cervix Cancer: Time for Change

  • M.A. Zahra

      Affiliations

    • Corresponding Author InformationAuthor for correspondence: M.A. Zahra, Edinburgh Cancer Centre, Western General Hospital, Edinburgh, UK.

Edinburgh Cancer Centre, Western General Hospital, Edinburgh, UK

Received 10 June 2010; accepted 14 June 2010. published online 09 August 2010.

Article Outline

 

The group for Cancer Care in Ontario have produced a document collating organisational and technical advice for the delivery of brachytherapy for cervical cancer. This document can serve as a template for departments in the process of switching from low dose rate (LDR) to high dose rate (HDR) or pulsed dose rate (PDR) systems and/or upgrading their brachytherapy facilities. The Ontario group have carried out an exhaustive search and identified 20 guidance documents coming from the leading radiotherapy and brachytherapy organisations. They used these as the evidence base for their final recommendations aimed at ensuring the delivery of high-quality brachytherapy.

Brachytherapy remains an integral part of the non-surgical treatment of cervical cancer. The ability to deliver a high radiation dose to a small volume over a short period of time contributes significantly to the chance of adequate tumour control while limiting the toxicity to the surrounding normal tissues. As a modality of treatment, brachytherapy has been around for over a century; in fact it was used within a year of the discovery of radium. The system of prescribing gynaecological brachytherapy has been well established for many decades, with the use of point A well entrenched in the teaching of oncology. This has served cervical cancer patients well, with a reasonable rate of cure achieved even for large tumours.

A comprehensive retrospective review of cervical cancer patients carried out by Perez et al. [1] identified that outcomes are determined by the stage, tumour bulk and the overall radiation dose delivered to the tumour. They showed that the higher the total dose of radiotherapy delivered the higher the likelihood of achieving tumour control with a corresponding higher risk of associated toxicity. The authors concluded that results could be improved by the use of novel radiation sensitisers and/or improved delivery of brachytherapy. Although the external beam radiotherapy treatment of cervical cancer has changed over the last 10 years, with more sophisticated planning and delivery, e.g. outlining of nodal areas [2] at risk to ensure adequate coverage and shielding, or the use of intensity-modulated radiotherapy [3], the gains have been mainly in terms of a reduction in toxicity. The widespread uptake of concurrent chemotherapy after the National Cancer Institute announcement did result in improved overall survival rates [4], but this was partly offset by increased levels of late toxicity [5], [6]. It is also well documented that the lack of brachytherapy is associated with a worse prognosis [7], [8], and although it has been shown that patients could still be potentially salvaged by the use of a phase 2 external beam boost [9] or even possibly by surgery [10], these are not real substitutes for intracavitary brachytherapy [11].

Because the industry will no longer provide or support LDR systems, many brachytherapy units have had to review their set-up and assess their patients’ requirements. The need to change from LDR to HDR or PDR brachytherapy systems has come at a propitious time when developments in the planning and delivery of brachytherapy for cervical cancer have caught up with developments in the field of external beam radiotherapy and led to the development of image-guided brachytherapy (IGBT). This was in particular driven by the GEC-ESTRO group [12], [13], who developed a series of recommendations regarding target volume outlining and dose constraints to the organs at risk.

The delivery of IGBT increases the complexity of cervical brachytherapy both from a clinical point of planning and delivery, and from a logistical point of getting access and availability to the required resources. This will have an effect on the working patterns of departments and the teams involved. So it is legitimate to ask whether this is justified in terms of improved outcomes that can be achieved using IGBT. Although several dosimetry papers [14], [15] show that IGBT can allow dose optimisation to improve the target volume cover and reduce the dose to the organs at risk, it is the clinical outcomes that are most important. It can be quite difficult to define a threshold at which increasing treatment complexity can be justified both in terms of investment in additional resources and also in terms of demands placed on the patients. In a small patient survey by Wright et al. [16], when patients were asked to choose between a single LDR insertion or multiple fractions of HDR, only 34% of patients opted for HDR. When faced with a hypothetical increase in survival of 2% or a decrease in toxicity of 6%, up to 50% of potential patients would have preferred to have the fractionated HDR treatment.

Evidence regarding the clinical outcome of cervical IGBT is now slowly accumulating. There are four publications from different cancer centres that have shown remarkably similar outcomes [17], [18], [19], [20] and one series has been published in abstract form [21]. Of note, they all showed improved local control, either by comparisons with pre-IGBT cohorts treated at the same institutions or with previously published data. The improved local control ranged between 2 and 26%. It was particularly relevant for bulky tumours (>5cm), which are known to respond poorly due to a variety of reasons, including poor coverage by the brachytherapy therapeutic isodoses and inherent radioresistance in hypoxic regions. The improved control is attributable to improved target coverage and the corresponding increased dose to the residual tumour. This was accompanied by a reduction of 3% to 11% in overall toxicity. What is interesting is that although all four series used different imaging techniques (magnetic resonance imaging/computed tomography/ultrasound) and prescriptions, the outcomes were broadly similar, indicating a proof of principle.

A robust quality assurance system is required with such a complex treatment involving a high activity source, the need to deliver a tailored treatment plan within a short time frame and a multidisciplinary team to produce a concerted effort. This will ensure a safe, consistent and high-quality treatment. The Ontario recommendations specify, among other things, that treatment planning must be carried out for each insertion. Other groups [22], [23] have shown the importance of dosimetry before each fraction due to the risk of interfraction variations, even for fixed geometry applicators. The recommendations of the Ontario group can help to formulate various aspects of a quality assurance system that could be adapted to the local needs and circumstances.

The recommendations also focus on the physical resources required to deliver the treatment, including the need for theatre access or a specifically designed brachytherapy suite that would help to minimise patient movement. They go into the use of three-dimensional imaging modalities that need to be considered; and although acknowledging the superiority of magnetic resonance imaging for outlining the target volume, they also recognise that timely access may be an issue — something that would be familiar to many other departments. On the other hand, access to computed tomography will be relatively easier, with scanners being available within most oncology departments. This has been shown that it is adequate for outlining of the organs at risk, but less accurate for target volume delineation, and the volumes have been shown to be consistently larger than for magnetic resonance imaging to compensate for the reduced accuracy [24]. There is also mention of the use of ultrasound to guide the insertion, which perhaps is an underutilised resource. Although most brachytherapists depend on their experience to correctly insert the applicators, ultrasound could help in the cervical cannulation of difficult cases. It could also provide real time verification of the applicator position and allow correction of suboptimal implants, which have been associated with poor clinical outcomes [25]. Ultrasound remains a relatively low cost imaging modality, and members of the brachytherapy team could be trained in its use to reduce the demand on radiology time.

The Ontario group also looked at the brachytherapy team members, and specify the roles and responsibilities of each of the different disciplines. There is acknowledgment of the increasing importance of image interpretation by the oncologist and the need for this to be incorporated in training programmes. There is also mention of the need for subspeciality training for brachytherapy and that this might not be available for all trainees. Treatment with brachytherapy requires technical competence, and these skills and competencies need to be maintained. There is published evidence [23] that outcomes are related to patient volumes, with larger centres seeing larger patient numbers doing better overall. The recommendation is that a team should do at least one procedure per month and treat a minimum of 10 patients a year. This is in keeping with similar recommendations by the Royal College of Radiologists [26]. This not only helps to maintain the technical competence required, but also reflects to an extent the number of patients required to provide a feasible brachytherapy service. With a decreasing incidence of cervical cancer, some centres seeing a very small number of patients might need to make provisions for referring these patients for their brachytherapy treatment elsewhere. Adequate planning of such referrals would be vital to ensure an acceptable overall treatment time. This could have the additional benefit that designated brachytherapy centres would have sufficient patient numbers to contribute to subspeciality training and further development of brachytherapy techniques.

The guidelines by the Ontario group provide a condensed summary of the available evidence and recommendations involved in setting up a robust and quality assured brachytherapy service. These recommendations have a wide applicability and reflect the situation in most UK departments, both in terms of the team and physical set-up, but also in the difficulties encountered in delivering the service. They provide a timely resource for departments in the process of upgrading their brachytherapy facilities, which might allow the more widespread uptake of IGBT.

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PII: S0936-6555(10)00267-0

doi:10.1016/j.clon.2010.07.011

Clinical Oncology
Volume 22, Issue 7 , Pages 602-604, September 2010

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