Vanessa N. Harry

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.

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.

Predicting the Response of Advanced Cervical and Ovarian Tumors to Therapy

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.

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.

Se acabaron las citologías con discariosis moderada

Objetivo. La British Society for Clinical Cytology ha propuesto recientemente una modificación de la terminología para los informes de frotis cervicales, pasando de un sistema de 3 tipos (discariosis leve, moderada o grave) a otro de dos tipos, denominados discariosis de bajo grado y de alto grado. Esta modificación elimina la categoría central de discariosis moderada que se incorporaría al grupo de alto grado. El objetivo de este estudio fue investigar el papel de las citologías con discariosis moderada en la práctica clínica. Material y métodos. Se llevó a cabo una revisión retrospectiva de todas las mujeres que fueron remitidas a una exploración colposcópica debido a una citología con discariosis moderada a lo largo de un periodo de 6 meses. Los datos recogidos incluyeron la impresión colposcópica, la intervención realizada y el diagnóstico histopatológico final. Se pidió a dos citólogos, que no conocían el informe inicial de las citologías, que volvieran a clasificarlos con el empleo del nuevo sistema de sólo dos clases. Se compararón sus resultados con los resultados documentados de la colposcopia e histopatología. Resultados. Un total de cien mujeres con citologías con discariosis moderada fueron remitidas a colposcopia durante el período de estudio. La mayoría de ellas fueron clasificadas en la categoría de discariosis de alto grado utilizando el nuevo sistema. En 56 (72%) de las citologías con discariosis moderada que fueron clasificados correctamente como de alto grado por el citólogo 1 se observó una neoplasia cervical intraepitelial 2‐3 en la histopatología final, mientras que en el caso del citólogo 2, en 66 (68%) se observó una neoplasia cervical intraepitelial de alto grado. Conclusión. La conservación del término de discariosis moderada no aporta ninguna ventaja clínica. Este estudio resalta la necesidad de utilizar un sistema uniforme de dos clases.

Auditoría del uso de una consulta de colposcopia frente a una consulta de ginecolog frente a una consulta de ginecología general en el estudio diagnóstico de mujeres con hemorragia poscoital o intermenstrual: argumentos a favor de un nuevo servicio ambulatorio

Objetivo. Esta auditoría tenía por objeto determinar el método de abordaje más eficiente, en las mujeres con hemorragia poscoital (HPC) o intermenstrual (HIM), si remitir inicialmente a una consulta de ginecología general (CGG) o a una consulta de colposcopia. Material y métodos. Se realizó una auditoría prospectiva de mujeres con una HPC o HIM. Sesenta pacientes remitidas desde la asistencia primaria fueron registradas y asignadas a una u otra clínica. Los datos se recogieron mediante una revisión de las historias clínicas. Resultados. Sesenta mujeres fueron remitidas por hemorragia anómala, 33 de ellas (55%) fueron atendidas en la CGG y 27 (45%), en la consulta de colposcopia. Los estudios diagnósticos consistieron en la prueba de clamidias, que fue insuficiente en ambos contextos, mientras que se realizó una ecografía e histeroscopia al 9% de las pacientes que acudieron a la CGG frente a ninguna en la clínica de colposcopia. El resultado más frecuente en la CGG fue el de una ectopia cervical en 14 pacientes (42%). En 9 pacientes (28%) no se detectó ninguna anomalía. En la colposcopia, no se detectó ninguna anomalía en 14 pacientes (52%), mientras que 8 (30%) presentaban una ectopia cervical y 3 (11%), una neoplasia cervical intraepitelial. En este estudio no se detectaron casos de cáncer. Conclusión. La mayoría de las pacientes con una HPC o HIM no presentarán una anomalía grave. Nuestro estudio propone que un nuevo servicio ambulatorio de HPC/HIM puede mejorar la eficacia del tratamiento de estas mujeres proporcionando directrices apropiadas para estandarizar su asistencia. ▪

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.