Robert Dinniwell MD, Presenter: Nothing to Disclose

Philip Chan, Abstract Co-Author: Nothing to Disclose

Michael Milosevic, Abstract Co-Author: Nothing to Disclose

Anthony Fyles, Abstract Co-Author: Nothing to Disclose

David Jaffray, Abstract Co-Author: Nothing to Disclose

Anna Kirilova, Abstract Co-Author: Nothing to Disclose

Lee Manchul, Abstract Co-Author: Nothing to Disclose

et al, Abstract Co-Author: Nothing to Disclose

Purpose/Objective: 3D-conformal and intensity-modulated radiation therapy (IMRT) delivery techniques have facilitated improvements in radiotherapy treatment precision and dose escalation. However, their potential is dependent upon accurate target delineation of both tumor and critical normal tissues. Each is susceptible to uncertainties such as reduction in tumor volume during treatment. The purpose of this study was to measure the temporal-spatial response of cervix cancer during a course of radiotherapy using serial MRI scans. In addition, the impact of tumor pO2 and interstitial fluid pressure (IFP) on disease regression was evaluated. Oxygenation and IFP have previously been demonstrated to have strong prognostic significance in cervix cancer independent of standard clinical prognostic factors (Fyles, 2002; Milosevic 2001). Materials/Methods: All patients with histopatholigcally proven carcinoma of the cervix who were eligible for radical chemo-radiotherapy were approached for this study. At the time of initial staging examination under anaesthetia, IFP was measured using a wick-in-needle apparatus and oxygen tension was measured using a polarographic needle electrode system (Eppendorf-Netheler-Hinz, Hamburg, Germany). Treatment consisted of 45 to 50 Gy in 1.8 to 2 Gy daily fractions delivered over 5 weeks using a 4-field technique and 18-to-25 MV photons. Cisplatin was administered weekly at a dose of 40 mg/m2. Upon completion of external beam radiotherapy (EBRT), patients received intra-uterine brachytherapy with a line source to a dose of 40 Gy at 2 cm from the centre of the stem. An initial pre-treatment MRI scan and weekly serial MRI scans were performed during EBRT. T2-weighted axial images were acquired at each time point using a General Electric 1.5 Tesla scanner. The Pinnacle3 treatment planning system was used to delineate gross tumor in each image set, defined as the region of high signal intensity in the cervix and adjacent tissues. The volume regression rate for each patient was determined by the slope of the linear regression line relating tumor volume to cumulative radiation dose. Results: Between July 2003 and November 2003, 6 patients with cervix cancer participated in the study. The median age at treatment was 47 years (range 40-62 years). The FIGO stage was 1B in 2 patients, 2B in 2 patients and 3B in 2 patients. The median pre-treatment tumor volume was 36.7 cm3 (range, 29.1-77.4 cm3). Tumor regression began early after the start of EBRT and was linearly related to cumulative dose. The Spearman correlation coefficients between tumor volume and dose in the 6 patients (5 or 6 data points for each case) ranged from -0.93 to -0.97 (p3/cGy, with a median value of 0.62 cm3/cGy. The dose to achieve a 50% reduction in initial high signal volume was between 18.8 and 47.1 Gy (median 26.2 Gy). Tumors with larger initial volumes appeared to regress more rapidly (Spearman r=0.7, p=0.1). However, there was no apparent relationship between the initial tumor volume and the residual volume at the completion of EBRT. Pre-treatment tumor oxygenation did not affect regression rate. However, tumors with high initial IFP regressed significantly more slowly than those with lower IFP (Spearman r=-0.9, p=0.037). Conclusions: MRI is useful as a means of documenting cervix cancer regression during a course of EBRT. Reduction in the volume of high signal intensity begins early and is linearly related to cumulative dose. Significant changes in tumor size and configuration may occur during EBRT. This has potentially important implications for optimized brachytherapy and IMRT treatment planning. In addition, the rate of regression determined in this manner may provide an important early indication of overall response to radiotherapy. Tumors with high IFP appear to regress more slowly in keeping with the results of our previous study that showed reduced local control and patient survival. Future work will build on these observations to better understand the role of serial MR imaging in the management of patients with cervix cancer.

Dinniwell, R, Chan, P, Milosevic, M, Fyles, A, Jaffray, D, Kirilova, A, Manchul, L, et al, , Utility of Magnetic Resonance Imaging Tumor Volumetry in Assessing Radiotherapy Response in Carcinoma of the Uterine Cervix.  Radiological Society of North America 2004 Scientific Assembly and Annual Meeting, November 28 - December 3, 2004 ,Chicago IL. http://archive.rsna.org/2004/4417986.html