Local recurrences in cervical cancer patients in the setting of image-guided brachytherapy: a comparison of spatial dose distribution within a matched-pair analysis

Abstract

Purpose: It has been shown that a cumulative dose of ≥87 Gy (EQD2) of external beam radiotherapy (EBRT) and image guided adaptive brachytherapy (IGABT) to the high risk clinical target volume (HR CTV) confer a local control rate >95% in locally advanced cervical cancer. This study examines the dose distribution within the HR CTV and intermediate (IR) CTV in patients with cervical cancer treated with definitive EBRT +/- concomitant chemotherapy and MRI-based IGABT between patients with local recurrence (LR) and patients in continuous complete local remission (CCLR).

Material and methods: From 1998 to 2010, 265 patients were treated with definitive EBRT +/- concomitant chemotherapy and IGABT. Twenty-four LRs were documented. For the statistical analysis all patients with LR were matched to patients in CCLR from our database according to the following criteria: FIGO stage, histology, lymph node status, tumour size and chemotherapy. DVH parameters (D50, D90, D98, D100) were reported for HR CTV and IR CTV. In order to report the minimum dose in the region where the recurrence occurred, the HR CTV/IR CTV were divided into four quadrants on transversal planes. The minimum dose at the HR CTV/IR CTV contour was measured (within the corresponding quadrant closest to the LR) in the treatment planning system. A mean minimum point dose (MPD) was calculated by averaging these measurements on four consecutive slices at the level of the recurrence for each of the 4 brachytherapy fractions. EQD2 doses were calculated by summation of all BT and external beam therapy fractions. For each matched patient in the control group the measurements were performed on the same quadrant and at the same level.

Results: Sufficient image data were available for 21 LRs. Eight central failures and 13 non-central failures were observed. The mean D90 and D100 for HR CTV were 77 Gy and 61 Gy for patients with LR and 95 Gy and 71 Gy for patients in CCLR, respectively (p<0.01). The MPD for HR CTV was 72 Gy for patients in the LR arm and 99 Gy for patients in the CCLR arm (p<0.01). In the LR arm seven patients had a D90 for HR CTV ≥87 Gy, however, in only three patients the MPD was ≥87 Gy.

Conclusion: This study demonstrated significant differences in local outcome according to the delivered dose. In 85% of the LRs systematic low dose regions with less than 87 Gy were found at HR CTV contour. Systematic low dose regions leading to local recurrence could be detected even if a D90 HR CTV ≥87 Gy was applied. In addition to DVH parameters, inspection of the spatial dose distribution remains a key point in dose prescription.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Figures

Fig. 1

Example of the assessment of the minimum point dose based on the case presented in Fig. 2. T2-weighted MR image from the first brachytherapy fraction. The local recurrence was located on the right pelvic wall. The point dose assessment was performed correspondingly in the right quadrant. The white arrow indicates the area of the minimum point dose.

Fig. 2

Example from the matched-pair analysis. Fig. 2a shows a patient from the local recurrence group and Fig. 2b shows the matched patient from the continuous complete remission group at the time of diagnosis (1), at the time of the first brachytherapy (BT) fraction (2) and with and without local recurrence (3). Both patients had a squamous cell carcinoma, staged as FIGO III with a maximum tumour diameter ⩾5 cm. Pelvic lymph nodes were involved in both cases. Both patients received concomitant cisplatin chemotherapy. The patient from Fig. 2a was treated with 45 Gy external beam radiotherapy (EBRT) and three fractions of intracavitary brachytherapy during the “learning period”. A substantial low dose region occurred in the right parametrial space. The local recurrence was located in the right pelvic wall corresponding to the low dose regions, as indicated by the white arrows. The D90 for HR CTV was 67.5 Gy and the MPD for HR CTV was 56.9 Gy. The patient from Fig. 2b was treated with 45 Gy EBRT and four fractions of combined intracavitary and interstitial BT. The HR CTV was sufficiently covered by the 7 Gy isodose-line. No local recurrence was reported until the time of analysis after a follow up time of 35 months. The D90 for HR CTV was 86 Gy and the MPD for HR CTV was 80 Gy. Black line – HR CTV. Inner white dotted line – 7 Gy isodose. Outer white dotted line – 5 Gy isodose.