Diffusion-weighted MRI to detect early response to chemoradiation in cervical cancer: A systematic review and meta-analysis.

OBJECTIVE: Diffusion-weighted magnetic resonance imaging (DWI) has shown promise in predicting response to therapy in several malignancies. This systematic review and meta-analysis aimed to evaluate DWI in the prediction of response to treatment in patients with cervical cancer. METHODS: A systematic search was conducted on PubMed, Web of Science, Cochrane and Google Scholar databases Studies that evaluated DWI and apparent diffusion coefficient (ADC) for response evaluation before, during and after treatment with a correlation to conventional response criteria were included. The primary endpoint was the mean ADC values of cervical cancer at these timepoints. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the quality of the studies. RESULTS: Nine studies, comprising 270 patients, were included. Pre-treatment ADC values showed no correlation with eventual response. However, in our meta-analysis, there was a significant correlation with early treatment ADC values obtained within the first 3 weeks of therapy and response, as well as a significant correlation with the percentage change in ADC (ΔADC) and response. In addition, the pooled mean ΔADC percentage was also significantly higher in responders than in non-responders (49.7% vs 19.7%, respectively, p = 0.016). CONCLUSION: DWI shows potential as a biomarker of early treatment response in patients with cervical carcinoma. Use of the change in ADC particularly within the first 3 weeks of therapy seems to be predictive of response and may serve as a suitable marker in the determination of early response.

Functional imaging for assessing tumor response in cancer of the cervix.

Treatment options for carcinoma of the cervix are guided by tumor stage, and include radical surgery, in cases where the tumor is confined to the cervix, or concurrent chemotherapy and radiotherapy. In those cases treated with chemoradiation, the ability to monitor the response to treatment in order to adapt the management plan during its course may be beneficial. This approach has the potential to offer an individualized treatment plan, allowing for differences in behavior between tumors to be addressed early, rather than a 'one size fits all' treatment approach. This article aims to review the use of evolving functional imaging techniques including diffusion-weighted MRI, dynamic contrast-enhanced MRI, and PET as tools for the evaluation of response to treatment of uterine cervical carcinoma.

The clinically suspicious cervix--how often is it cancer?

OBJECTIVE: To evaluate the outcome of women referred to colposcopy with the clinical finding of suspected cancer ("clinically suspicious cervix"). MATERIALS AND METHODS: A prospective cohort study of women referred to a dedicated colposcopy clinic serving a regional population with a clinically suspicious cervix was conducted. All referral letters were reviewed, and women were identified prospectively when the letter stated "referral for a clinically suspicious cervix." Relevant data were collected subsequently by case note review. RESULTS: One hundred four women were identified, and 95 attended for colposcopy from September 2006 to January 2008. Nine women defaulted. Seventy-six (80%) had a normal cervix or a benign cervical pathological result. Cervical intraepithelial neoplasia was detected in 15 patients (16%), and only 4 women (4%) had invasive cancer confirmed. CONCLUSIONS: We believe that women referred with a clinically suspicious cervix should be assessed in a general gynecology clinic rather than colposcopy because most will not have cancer. The small number of women with a clinical cancer can then be referred onto colposcopy, whereas women with benign pathological result can be treated appropriately in the general clinic.

Use of new imaging techniques to predict tumour response to therapy.

Imaging of tumour response to therapy has steadily evolved over the past few years as a result of advances in existing imaging modalities and the introduction of new functional techniques. The use of imaging as an early surrogate biomarker of response is appealing, because it might allow for a window of opportunity during which treatment regimens can be tailored accordingly, depending on the expected response. The clinical effect of this would ultimately result in a reduction in morbidity and undue costs. The aim of this review is to describe the potential of various new imaging techniques as biomarkers of early tumour response. We have reviewed the literature and identified studies that have assessed these techniques, such as diffusion-weighted MRI, dynamic contrast-enhanced MRI, magnetic resonance spectroscopy, and 18-fluorodeoxyglucose-PET as early response indicators, and highlight the current clinical awareness of their use.

Novel imaging techniques as response biomarkers in cervical cancer.

The use of novel imaging techniques that have the ability to evaluate tumour biology and function shows a great deal of promise in providing early surrogate biomarkers of response to therapy which may allow for individualised or patient-specific regimes. This would have considerable clinical benefit in allowing for a treatment regimen tailored accordingly to meet the expected response, thereby reducing morbidity. Several of these imaging modalities such as dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted MRI (DW-MRI), MR spectroscopy (MRS) and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) are now being introduced into the field of gynaecological oncology, with the majority of work being performed on cervical tumours. This review examines the use of these functional imaging techniques as response biomarkers in cervical cancer.

A combined pharmacokinetic and radiologic assessment of dynamic contrast-enhanced magnetic resonance imaging predicts response to chemoradiation in locally advanced cervical cancer.

PURPOSE: To investigate the combination of pharmacokinetic and radiologic assessment of dynamic contrast-enhanced magnetic resonance imaging (MRI) as an early response indicator in women receiving chemoradiation for advanced cervical cancer. METHODS AND MATERIALS: Twenty women with locally advanced cervical cancer were included in a prospective cohort study. Dynamic contrast-enhanced MRI was carried out before chemoradiation, after 2 weeks of therapy, and at the conclusion of therapy using a 1.5-T MRI scanner. Radiologic assessment of uptake parameters was obtained from resultant intensity curves. Pharmacokinetic analysis using a multicompartment model was also performed. General linear modeling was used to combine radiologic and pharmacokinetic parameters and correlated with eventual response as determined by change in MRI tumor size and conventional clinical response. A subgroup of 11 women underwent repeat pretherapy MRI to test pharmacokinetic reproducibility. RESULTS: Pretherapy radiologic parameters and pharmacokinetic K(trans) correlated with response (p < 0.01). General linear modeling demonstrated that a combination of radiologic and pharmacokinetic assessments before therapy was able to predict more than 88% of variance of response. Reproducibility of pharmacokinetic modeling was confirmed. CONCLUSIONS: A combination of radiologic assessment with pharmacokinetic modeling applied to dynamic MRI before the start of chemoradiation improves the predictive power of either by more than 20%. The potential improvements in therapy response prediction using this type of combined analysis of dynamic contrast-enhanced MRI may aid in the development of more individualized, effective therapy regimens for this patient group.

Predicting the response of advanced cervical and ovarian tumors to therapy.

UNLABELLED: The management of advanced cervical and ovarian cancers remains a significant challenge as many women fail to respond to recommended therapy, resulting in disease progression and ultimately patient death. Because of tumor heterogeneity, it is rare for all cancers of a particular type to respond to a specific therapy; and, as a result, many patients receive treatment from which they derive little or no benefit, leading to increased morbidity and undue costs. A marker that could rapidly predict or forecast disease outcome would clearly be beneficial in allowing the administration of a tailored regime for each patient while reducing toxicity and cost. Traditional prognostic factors of tumor size, grade, and stage are not ideal for predicting patient outcome, whereas the use of in vitro assays to detect chemosensitivity or resistance has not yet translated into routine clinical practice. Similarly, biomarkers and tumor markers vary in their predictive ability. DNA array technology offers great promise in predicting the response to therapy based on gene expression profiles, and can allow for targeted therapies against specific molecular alterations that cause disease. Imaging techniques, particularly those with the ability to characterize biological tissues and provide functional, structural, and molecular information, have the potential to noninvasively integrate physical and metabolic information. These include F-18-fluorodeoxyglucose positron emission tomography, dynamic contrast-enhanced magnetic resonance imaging, and diffusion weighted magnetic resonance imaging, all techniques that attempt to evaluate and predict therapy response and so influence clinical outcome. This review examines different methods of predicting the response to treatment in advanced cervical and ovarian tumors. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to describe why prediction of response to therapy for cervical and ovarian cancers is important, describe obstacles to use of in vitro assays to predict outcomes for therapy for ovarian and cervical cancers, and explain potentially new predictive markers.

Magnetic resonance imaging in gynecological oncology.

Magnetic resonance imaging (MRI) has become an indispensable tool in the assessment of malignant disease. With increasingly sophisticated systems and technical advancements, MRI has continued to expand its role in providing crucial information regarding cancer diagnosis and management. In gynecological malignancies, this modality has assumed greater responsibility, particularly in the evaluation of cervical and endometrial cancers. In addition to conventional imaging, innovative techniques such as dynamic contrast-enhanced MRI and diffusion-weighted MRI show promise in offering early assessment of tumor response. This paper reviews the current role of MRI in gynecological cancers and highlights the potential of novel techniques in improving patient care.

Diffusion-weighted magnetic resonance imaging in the early detection of response to chemoradiation in cervical cancer.

OBJECTIVE: To investigate diffusion-weighted magnetic resonance imaging (DWI) as an early and reproducible response indicator in women receiving concurrent radiotherapy and chemotherapy (chemoradiation) for advanced cervical cancer. METHODS: Twenty women with advanced cervical cancer were included in a prospective cohort study. DWI was carried out prior to chemoradiation, repeated after 2 weeks of therapy and at the conclusion of therapy using a 1.5 T MRI scanner. The apparent diffusion coefficient (ADC) was calculated from the diffusion data at each assessment. This was correlated with final tumour response as determined by change in tumour size using MRI and conventional clinical response. Twelve women also underwent 2 separate pre-treatment DWI examinations to test for reproducibility of the ADC measurements. RESULTS: ADC values after 2 weeks of therapy showed a significant correlation with eventual MR response (p=0.048, rho=0.448, Spearman's correlation) and clinical response (p=0.009, rho=0.568) as did the change in ADC after 2 weeks of therapy (p=0.01, rho=0.56 for MR response, p=0.03, rho=0.48 for clinical response). Reproducibility of ADC measurements was confirmed with a mean difference in ADC of -0.003 between consecutive pre-therapy MRI assessments and 95% confidence intervals of -0.12 and 0.11. CONCLUSION: DWI has potential to provide a surrogate biomarker of treatment response in advanced cervical cancers. The use of ADC offers an early and reproducible indication of tumour response which may ultimately allow the development of individualised regimens.

Is this the end of the line for the moderate dyskaryotic smear?

OBJECTIVE: The British Society for Clinical Cytology has recently proposed that the terminology for cervical smear reporting is to be changed from a 3-tier system (mild, moderate, severe dyskaryosis) to a 2-tier system of low-grade and high-grade dyskaryosis. This modification eliminates the central category of moderate dyskaryosis which would be incorporated into the high-grade group. The aim of this study was to investigate the role of the moderate dyskaryotic smear in clinical practice. MATERIALS AND METHODS: A retrospective review of all women who were referred for colposcopy because of a moderate dyskaryotic smear was carried out for a 6-month period. Data collected included colposcopic impression, procedure performed and final histopathology. Two cytologists who were unaware of the original smear report were asked to reclassify these smears using the new 2-tier system. Their findings were compared with the documented colposcopic and histopathology results. RESULTS: One hundred women with moderate dyskaryotic smears were referred for colposcopy during the study period. Most of these were reclassified as high-grade dyskaryosis using the new system. Fifty-six (72%) of the moderate dyskaryotic smears which were correctly regraded as high grade by cytologist 1 were found to have cervical intraepithelial neoplasia 2/3 on final histopathology, whereas for cytologist 2, 66 (68%) were found to have high-grade cervical intraepithelial neoplasia. CONCLUSION: There is no clinical benefit in retaining the term moderate dyskaryosis. This study emphasizes the need for a uniform 2-tier system.

Isolated clear cell adenocarcinoma in scar endometriosis mimicking an incisional hernia.

BACKGROUND: The development of a mass in association with a previous surgical scar can pose a diagnostic dilemma due to similarities in appearance to hernias, abscesses, hematomas, or desmoid tumors. Scar endometriosis is an uncommon cause of such a lump, but malignant change within this ectopic tissue is exceptionally rare. CASE: We present a case of a 55-year-old woman who was found to have an isolated clear cell adenocarcinoma in an area of scar endometriosis more than 30 years after an open tubal sterilization. This mass was initially thought to be an incisional hernia, but was later diagnosed intraoperatively by frozen section and then incompletely excised, highlighting the difficulties in preoperative diagnosis as well as surgical treatment. CONCLUSION: Malignant change within scar endometriosis is rare, but increased awareness of this phenomenon is required. Vigilance is paramount and a mass located in or close to a surgical scar should be treated with suspicion.

Auditing the use of colposcopy versus general gynecology clinics to investigate women with postcoital or intermenstrual bleeding: a case for a new outpatient service.

OBJECTIVE: The aim of this audit was to determine whether initial referral to a general gynecology clinic (GOPD) or a colposcopy clinic is the most efficient means of managing women with postcoital (PCB) or intermenstrual (IMB) bleeding. MATERIALS AND METHODS: A prospective audit of women with PCB or IMB was conducted. Sixty referrals from primary care were note-logged and alternatively allocated to either clinic. Data were collected by case note review. RESULTS: Sixty women were referred for abnormal bleeding, 33 (55%) of which were seen at the GOPD and 27 (45%) at the colposcopy clinic. Investigations included Chlamydia testing, which was deficient in both settings, whereas ultrasound scans and hysteroscopies were performed in 9% of patients attending the GOPD compared with none in the colposcopy clinic. The most common finding at the GOPD was cervical ectopy in 14 (42%) patients. No abnormality was found in 9 (28%) patients. At colposcopy, 14 (52%) had no abnormality detected, whereas 8 (30%) had cervical ectopy and 3 (11%) had cervical intraepithelial neoplasia. There were no cases of malignancy found in this study. CONCLUSION: Most patients with PCB and IMB will not have a serious abnormality. Our study proposes that a new PCB/IMB outpatient service can improve the efficiency of treatment of these women by providing appropriate guidelines to standardize their care.