Melanie Powell

An assessment of interfractional uterine and cervical motion: implications for radiotherapy target volume definition in gynaecological cancer.

PURPOSE To assess interfractional movement of the uterus and cervix in patients with gynaecological cancer to aid selection of the internal margin for radiotherapy target volumes. METHODS AND MATERIALS Thirty-three patients with gynaecological cancer had an MRI scan performed on two consecutive days. The two sets of T2-weighted axial images were co-registered, and the uterus and cervix outlined on each scan. Points were identified on the anterior uterine body (Point U), posterior cervix (Point C) and upper vagina (Point V). The displacement of each point in the antero-posterior (AP), superior-inferior (SI) and lateral directions between the two scans was measured. The changes in point position and uterine body angle were correlated with bladder volume and rectal diameter. RESULTS The mean difference (+/-1 SD) in Point U position was 7 mm (+/-9.0) in the AP direction, 7.1 mm (+/-6.8) SI and 0.8 mm (+/-1.3) laterally. Mean Point C displacement was 4.1 mm (+/-4.4) SI, 2.7 mm (+/-2.8) AP, 0.3 (+/-0.8) laterally, and Point V was 2.6 mm (+/-3.0) AP and 0.3 mm (+/-1.0) laterally. There was correlation for uterine SI movement in relation to bladder filling, and for cervical and vaginal AP movement in relation to rectal filling. CONCLUSION Large movements of the uterus can occur, particularly in the superior-inferior and anterior-posterior directions, but cervical displacement is less marked. Rectal filling may affect cervical position, while bladder filling has more impact on uterine body position, highlighting the need for specific instructions on bladder and rectal filling for treatment. We propose an asymmetrical margin with CTV-PTV expansion of the uterus, cervix and upper vagina of 15 mm AP, 15 mm SI and 7 mm laterally and expansion of the nodal regions and parametria by 7 mm in all directions.

Cediranib combined with carboplatin and paclitaxel in patients with metastatic or recurrent cervical cancer (CIRCCa): a randomised, double-blind, placebo-controlled phase 2 trial

Summary Background Patients treated with standard chemotherapy for metastatic or relapsed cervical cancer respond poorly to conventional chemotherapy (response achieved in 20–30% of patients) with an overall survival of less than 1 year. High tumour angiogenesis and high concentrations of intratumoural VEGF are adverse prognostic features. Cediranib is a potent tyrosine kinase inhibitor of VEGFR1, 2, and 3. In this trial, we aimed to assess the effect of the addition of cediranib to carboplatin and paclitaxel chemotherapy in patients with metastatic or recurrent cervical cancer. Methods In this randomised, double-blind, placebo-controlled phase 2 trial, which was done in 17 UK cancer treatment centres, patients aged 18 years or older initially diagnosed with metastatic carcinoma or who subsequently developed metastatic disease or local pelvic recurrence after radical treatment that was not amenable to exenterative surgery were recruited. Eligible patients received carboplatin AUC of 5 plus paclitaxel 175 mg/m2 by infusion every 3 weeks for a maximum of six cycles and were randomised centrally (1:1) through a minimisation approach to receive cediranib 20 mg or placebo orally once daily until disease progression. The stratification factors were disease site, disease-free survival after primary therapy or primary stage IVb disease, number of lines of previous treatment, Eastern Cooperative Oncology Group performance status, and investigational site. All patients, investigators, and trial personnel were masked to study drug allocation. The primary endpoint was progression-free survival. Efficacy analysis was by intention to treat, and the safety analysis included all patients who received at least one dose of study drug. This trial is registered with the ISCRTN registry, number ISRCTN23516549, and has been completed. Findings Between Aug 19, 2010, and July 27, 2012, 69 patients were enrolled and randomly assigned to cediranib (n=34) or placebo (n=35). After a median follow-up of 24·2 months (IQR 21·9–29·5), progression-free survival was longer in the cediranib group (median 8·1 months [80% CI 7·4–8·8]) than in the placebo group (6·7 months [6·2–7·2]), with a hazard ratio (HR) of 0·58 (80% CI 0·40–0·85; one-sided p=0·032). Grade 3 or worse adverse events that occurred in the concurrent chemotherapy and trial drug period in more than 10% of patients were diarrhoea (five [16%] of 32 patients in the cediranib group vs one [3%] of 35 patients in the placebo group), fatigue (four [13%] vs two [6%]), leucopenia (five [16%] vs three [9%]), neutropenia (10 [31%] vs four [11%]), and febrile neutropenia (five [16%] vs none). The incidence of grade 2–3 hypertension was higher in the cediranib group than in the control group (11 [34%] vs four [11%]). Serious adverse events occurred in 18 patients in the placebo group and 19 patients in the cediranib group. Interpretation Cediranib has significant efficacy when added to carboplatin and paclitaxel in the treatment of metastatic or recurrent cervical cancer. This finding was accompanied by an increase in toxic effects (mainly diarrhoea, hypertension, and febrile neutropenia). Funding Cancer Research UK and AstraZeneca.

A verification study of proposed pelvic lymph node localisation guidelines using nanoparticle-enhanced magnetic resonance imaging.

BACKGROUND AND PURPOSE Normal sized pelvic lymph nodes are not easily identifiable on conventional imaging, but can be visualised with contrast-enhanced magnetic resonance imaging (MRI) using intravenous ultra-small particles of iron-oxide (USPIO). We have previously reported pelvic node clinical target volume (CTV) delineation guidelines for use with conventional imaging, derived from nodal mapping studies using USPIO. This study aims to verify these guidelines using an independent observer in a further patient cohort. MATERIALS AND METHODS Ten patients with gynaecological cancer underwent MRI with and without intravenous USPIO. The guidelines were used to outline a pelvic node CTV on pre-contrast T2-weighted images. On post-contrast T2-weighted images the pelvic nodes were identified and outlined. The pre- and post-contrast images were co-registered and CTV examined for node coverage. RESULTS By applying the guidelines, full coverage of 737 of 741 node outlines was achieved (>99%). Four nodes were not completely encompassed, two anterior external iliac nodes and two lateral external iliac nodes. CONCLUSIONS MRI with USPIO contrast enabled the production of guidelines for localising a pelvic node CTV with conventional imaging. Application of these guidelines to a further patient cohort resulted in coverage of 99.5% node outlines demonstrating the reliability of this technique.

Conformal and Intensity-modulated Radiotherapy for Cervical Cancer

Three-dimensional radiotherapy planning techniques, including conformal radiotherapy and intensity-modulated radiotherapy, have potential for improving outcomes in cervical cancer. Accurate target volume definition is essential in order to maximise normal tissue sparing while minimising the risk of a geographical miss. This reduction in toxicity provides the option of dose escalation, particularly with simultaneous integrated boost intensity-modulated radiotherapy. The evidence for the current use and potential applications of these techniques in the treatment of cervical cancer are discussed.

The Role of Postoperative Radiotherapy in Carcinoma of the Endometrium

The role of adjuvant postoperative radiotherapy in endometrial carcinoma after surgery remains controversial. There is a great variation between centres in deciding when to give postoperative external beam radiotherapy and/or vaginal vault brachytherapy for patients with endometrial carcinoma. The role of pelvic and para-aortic lymphadenectomy as well as the need for postoperative radiotherapy after this type of surgical staging continue to be debated. Furthermore, the role of adjuvant chemotherapy either alone or in combination with adjuvant radiotherapy also remains to be determined. This overview discusses the role of postoperative radiotherapy in the context of surgery and other adjuvant treatments in carcinoma of the endometrium.

Radiation hazards in pregnancy and methods of prevention.

The incidence of malignancy in pregnancy is low and most commonly occurs in breast, gynaecological, skin and haematological sites. The management of pregnant cancer patients is complex requiring a multidisciplinary approach to ensure the welfare of both mother and baby. Foetal radiation exposure, both diagnostic and therapeutic, must be kept to a minimum. Following the description of the deterministic and stochastic effects of foetal radiation exposure doses, radiotherapy should be avoided in the first and early second trimester. This chapter describes the possible diagnostic techniques and treatment for the common malignancies in pregnancy; some case studies indicating supradiaphragmatic radiotherapy may be safe later in pregnancy. Pelvic radiotherapy for gynaecological malignancies is not appropriate.

First Quinquennial Review of Intensity-modulated Radiotherapy at St Bartholomew's Hospital, London

Intensity-modulated radiotherapy (IMRT) is a relatively new technique of delivering external beam radiotherapy that is becoming increasingly available in the UK. This paper summarises the introduction and initial clinical work in IMRT over the period 2004-2009. Physics aspects of commissioning are described, including the development of a robust method of quality control using a sweeping gap test. Details of the organisational changes necessary to introduce IMRT are given. The clinical selection and practice in head and neck sites are described, together with promising early results on the maintenance of salivary flow after IMRT. A summary of research into optimal planning for pelvic cancer follows. The controversial areas of breast and paediatric IMRT are discussed with recommendations on practice. The potential for concomitant boost therapy is exemplified in the treatment of brain metastatic disease.

Nonurological Cancers Affecting the Urinary Tract

Many pelvic malignancies that are not part of the urinary tract none the less impact on it. This is in part because they are in close anatomical proximity in particular to the ureters which if compromised may lead to renal failure. In addition the morbidity of surgical, chemotherapy and radiotherapy treatments of these malignancies can also affect the urinary tract. This chapter will outline the incidence, staging and management of cancers of the uterus, cervix, colon, rectum and lymphomas with particular reference to their impact on the urinary tract.