Pre-operative CT scan in breast conserving therapy for more accurate radiation boost volume delineation.

In the Netherlands, yearly about 12000 women are diagnosed with invasive breast
cancer. Of these, almost 1300 women are diagnosed with carcinoma in situ (Dutch
Cancer registration, NKR). The lifetime chance for women developing breast
cancer is 12-13%. Treatment for breast cancer patients is a rapidly changing
field. In 2002 the first Dutch multidisciplinairy guideline for breast cancer
treatment appeared. The treatment guideline was renewed in 2005 and 2008.
(breast cancer guideline 2005 and 2008)
Since the 90*s the majority of women with breast cancer are treated with breast
conserving therapy. Several randomised trials show no difference in survival
between breast conserving therapy and modified radical mastectomy for early
breast cancer (stage T1-2 ). (Jacobson et al, 1995; Fisher et al,1995; Sarrazin
et al, 1989; van Dongen et al, 2000; Veronesi et al, 1995).
Radiotherapy as part of breast conserving treatment consists of radiation of
the whole breast and a boost dose to the tumour excision area. This boost dose
can be given as a simultaneous integrated boost or sequentially after radiation
of the whole breast. Results of the boost versus no boost trial show, after 10
years follow up a 50% decrease of local failure in favour of the group treated
with a boost. (Bartelink et al, 2007). This is independent of the systemic
adjuvant given therapy.

Combining different imaging modalities (Magnetic Resonance Imaging (MRI),
Computed Tomography (CT), ultrasound and mammography) can give reliable
information on the place and extension to the tumour. This imaging serves as a
guide for the surgical excision; moreover, preoperative imaging is used for
defining the radiotherapy boost volume more precisely. During the operation the
surgeon places one or more clips in the excisional cavity. These clips are
mostly situated at the deepest point of the excision cavity, but also clips
spread around the excision cavity are seen. Defining the boost volume is done
by using pre-operative palpation of the tumour, pre-operative imaging, the
operatively placed clips and the postoperative CT scan.
Despite of all this information, in practice a great uncertainty of the
position of the original tumour exists, leading to interobserver variety in
delineation of the target volume. In a trial with five observers and 18
patients a conformity index of 0.56 was found (range 0.37-0.74). This indicates
that among the participants there was agreement on only slightly more than half
of the delineated volume. (Struikmans et al, 2005). In light of these
uncertainties a relative large uncertainty margin is taken for the definitive
boost irradiation.

Currently, a postoperative simulation CT scan is used for a dose calculation of
the radiotherapy boost. This gives more accurate (3D) information on dose
homogeneity and dose to critical organs (lung, heart and contralateral breast)
than dose calculations using conventional simulation (under fluoroscopy
images). However, several studies have shown that using a CT-based planning can
result in 1.29 to 1.6 times larger volumes than the conventional boost
simulation calculations. (Hanbeukers et al, 2009, van der Laan et al, 2008).

The boost versus no boost trial shows that in the no boost group 86% of
patients had an excellent or good global cosmetic outcome. In the boost group
this was significantly less with 71% (Vrieling et al, 1999). Besides the boost
other significant factors influencing cosmesis are a caudal localisation of the
tumour, a larger excision volume and postoperative complications (Vrieling et
al, 2000). Previous studies have shown that radiation volume and radiation dose
are also factors which significantly effect the cosmetic outcome. (van
Limbergen et al, 1989; Borger et al, 1994).

Dynamic contrast enhanced CT scan of the breast seems to be effective for
detecting intraductal extension of breast cancer. A pre-operative CT scan has
also shown to be useful for pre-operative assessment for suitability of breast
conserving treatment (Yamamoto et al, 2006). The tumour is visible on CT as a
dense lesion and shows early contrast enhancement as seen in dynamic MRI. CT is
less sensitive than a mammography for detecting microcalcifications, if this is
the only sign of early breast cancer (Ternier et al, 2006).

The location of the original tumour is difficult to define on a postoperative
CT scan. When a pre-operative CT scan in radiotherapy position is performed,
the tumour may serve as a base for determination of the boost area on the
postoperative scan, (Clinical Target Volume (CTV), when the pre-operative scan
is matched with the postoperative scan. Possibly the CTV can be defined more
accurately which could lead to a decrease of the boost volume.
Possible contour change of the breast due to surgery should be taken in
consideration.

The purpose of this study is to investigate whether the pre-operative contrast
enhanced CT scan can be used for determination of the pre-operative tumour
localisation, with the aim of increasing the accuracy of the boost area. If so,
the boost volume might possibly be decreased. The usefulness of the
pre-operative CT scan for this aim partly depends on the question in what
percentage of patients the tumour is clearly visible on this scan and of the
possibility of matching the pre-operative CT scan with the simulation CT scan.
In other words, does the lumpectomy cause a contour change of the breast, which
makes the pre-operative CT scan unusable.

All women with stage T1-3, N0-2 breast cancer, pre-operatively seen in the
radiotherapy department, can be asked to join this study. After written
informed consent, patients will have a pre-operative CT scan in radiation
position after intravenous contrast has been given. The simulation CT scan will
preferably made 3-4 weeks after surgery, without contrast.

Pre operative CT scan will be performed with the following conditions:
* CT scan (GE, The LightSpeed® RT16)
* 2.5 mm slides
* Radiotherapy position, indicating supine on a C-Qual breast board (CIVCO
medical solutions)
* Iv contrast (Otiray® 350, Mallinckrodt Medical B.V.) 90 ml
* Isocenter marking by using a lead coil and a tattoo point
* Marking the breast glandular tissue by electra wire

There will be a minimal additional X-ray exposure, which is negligible compared
to the radiation exposure due to radiotherapy. There is also a minimal risk of
side effects of the intravenous contrast.



Stopping rule
If it appears that after 5 scanned patients, on 3 or more patients the tumour
is not visible on the pre-operative CT scan, the study will be discontinued.