Diffusion-weighted magnetic resonance imaging in the early detection of response to chemoradiation in cervical cancer
Introduction
One of the greatest challenges in cancer management is to develop a method of rapidly and objectively measuring tumour response to therapy. A reliable and early marker of response would have immense clinical value as persisting with ineffective treatment is associated with increased toxicity and morbidity as well as delays in commencing alternative, potentially effective treatment. Inappropriate therapy may also result in accelerated tumour growth and development of drug-resistance, while incurring unnecessary expense. Current conventional imaging techniques used to assess and monitor response rely on identifying anatomical and morphological criteria with changes in tumour dimension defining response or progression. These changes in gross tumour size significantly lag behind the biological and molecular changes that occur early in responders [1], [2], [3]. Due to tumour heterogeneity, it is unlikely that all cancers of a particular type will respond to a specific therapy [4], [5], emphasising the need for a reliable and early marker of tumour response which would enable the development of customised regimes.
Novel imaging techniques that integrate morphological and functional changes offer great promise as early indicators of therapy response. Diffusion-weighted magnetic resonance imaging (DWI) has been explored in the imaging of cerebral stroke and in the detection of early changes in response to therapy [6], [7]. DWI is sensitive to the microscopic motion of water molecules and allows for non-invasive characterisation of biological tissues based on their water diffusion properties [8], [9], [10]. By applying diffusion-weighted gradient pulses to a conventional magnetic resonance sequence [11], the signal can be made sensitive to the level of localised water diffusibility that can be quantified as the apparent diffusion coefficient (ADC). It has been suggested that DWI can be used as a surrogate biomarker of tumour cellularity by observing the water mobility within tumours [10], [12], [13], [14], [15]. Following successful anti-cancer treatment, alterations in cell density due to necrosis and apoptosis cause significant changes in water diffusion which are detectable by DWI. In addition, these changes in water mobility occur well before macroscopic indicators of response such as tumour size or volume [2], [16].
DWI has gained attention in several preclinical models as an early and sensitive biomarker of tumour response to therapy as well as survival [12], [13], [16], [17], [18], [19], [20]. This has fuelled enthusiasm for the use of DWI in clinical scenarios where preliminary results from studies involving brain [21], [22], [23], breast [24], [25] and rectal tumours [26], [27] have been promising. This modality however has not yet been explored in gynaecological tumours as an early biomarker of response. We conducted a prospective cohort study to investigate the use of DWI as an early and reproducible predictor of response in women receiving chemoradiation for advanced cervical cancers. Our hypothesis was that ADC, and the change in ADC as a result of therapy, could provide a marker of early response in a gynaecological malignancy.
Section snippets
Patients and treatment
Consecutive women presenting to the regional oncology centre with advanced cervical cancer between May 2006 and October 2007 were invited to participate. As Aberdeen Royal Infirmary is the only oncology centre for the Grampian Region this referral was population based. Inclusion criteria were women of all ages with biopsy-proven untreated cancer of the cervix (including squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma), clinically staged as the International Federation of
Results
Twenty-five suitable women with advanced cervical cancer presented to our unit during the study period. Two women did not receive cisplatin chemotherapy due to renal disease and one woman who was severely claustrophobic was excluded. A further 2 opted out of the study for personal reasons. Of the remaining 20 women, 18 (90%) of these had a squamous cell carcinoma and 2 (10%) had an adenocarcinoma (mean age of 50 years with a range of 34–80). One woman was clinically staged as FIGO stage IB2, 2
Discussion
We have demonstrated the potential of using ADC measurements, obtained as early as 2 weeks into a treatment regime, in the detection of early tumour response in women receiving chemoradiation for advanced cervical cancer. We were able to demonstrate reproducibility of ADC measurements by performing an additional MR examination in 12 women and subsequently using a Bland–Altman plot [30] to confirm repeatability of these measurements. Similarly, we have shown that the 2 separate assessments of
Conflict of interest statement
The authors have no conflicts of interest to declare.
Acknowledgments
We are grateful to NHS Research and Development Department for their assistance in providing funding to cover the cost of the MRI examinations.
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