Search

This study aimed to assess the dosimetric impact of setup errors during the delivery of radiotherapy to the breast, and use this information to make recommendations on intervention tolerances for portal imaging of breast treatments. Translational and rotational setup errors were simulated for 10 recent breast patients using an Oncentra MasterPlan treatment planning system. The effect of these errors on the breast and tumor bed target volumes receiving 95% and 107% of the prescribed dose were assessed. For the majority of patients, shifts of up to 10 mm or a 4 degrees patient rotation about the cranio-caudal axis had no significant effect on the dose distribution. Changes in dosimetry were more likely if the reference plan contained large hot or cold spots. For a typical patient, it is estimated that a shift of 5 mm in any one direction, or a 2 degrees patient rotation would not cause more than a 5% change in the target volume receiving between 95% and 107% of the prescribed dose. If combinations of errors occur, greater dosimetric changes would be expected. It is concluded that individual patient shifts of up to 5 mm or rotations about the cranio-caudal axis of 2 degrees or less are unlikely to affect dose-volume histogram parameters by an amount judged as clinically significant. Setup errors exceeding these values may cause large dosimetric changes for some patients, particularly those with larger hot or cold regions in the dose distribution, and intervention is therefore recommended.

Radiotherapy treatment planning calculations of the chest wall are complex due to missing tissue, the thin chest wall and the presence of lung. The accuracy of calculated dose is dependent on the type of algorithm employed. This work evaluates a collapsed cone (CC) and a pencil beam (PB) convolution model for radiotherapy planning of the chest wall. Various irradiation geometries simulating the chest wall have been examined and calculations were compared with measurements with an ionization chamber in epoxy resin water substitute and in low-density lung substitute blocks. A retrospective treatment planning study comprising 6 patients was carried out to evaluate the differences in the dose distributions and monitor units predicted by the two algorithms. The calculated dose in unit density medium was within +/-1% for the CC model and up to +/-2% for PB. In low density medium and under full scatter conditions, CC overestimated the dose by 1% whereas PB overestimated the dose by 9%. In the tangential irradiation geometry with water and lung media, the PB overestimated dose to the isocentre by up to 10%, whereas the dose from CC was within 3%. From the treatment planning study calculated monitor units (MU) and doses were consistent with the experimental findings. The CC model is more accurate for radiotherapy treatment planning of the chest wall and especially when there is significant involvement of lung tissue.

Over a period of 6 1/2 years between January 1986 and May 1992, 135 unselected primary breast cancers were cultured and of these 10 developed into cell lines. Six of the lines grew in defined serum-free medium, while the other four required supplementation with 0.5% fetal calf serum. Two of the lines are from the same breast, being derived from a local excision specimen and from a mastectomy specimen 12 months later. In addition, 12 lymph nodes containing metastatic breast cancer were cultured; one of these cultures became permanent in a defined serum-free medium. Oestrogen receptor (ER) status was negative in all but one of the tumours which grew successfully, and even in this case the derived cell line is ER negative. The epithelial nature of the lines has been confirmed by immunocytochemistry and by electron microscopy (EM), while their malignant nature is shown by morphology, unattached growth, chromosome analysis, and, in the case of the line from a lymph node metastasis, the absence of any benign source of epithelial cells.

The DNA topoisomerase enzymes are targets for the cytotoxic effects of a number of anticancer agents termed topoisomerase inhibitors. We have analysed breast cancer biopsy specimens for genetic alterations at and around topoisomerase loci in order to obtain molecular insight into factors which may determine how tumours respond to chemotherapy. We show that of 50 tumours examined, the topoisomerase II alpha locus is co-amplified in 3 cases out of 6 with erbB2 amplification and that amplification can be accompanied by high expression of topoisomerase II alpha. In our attempts to distinguish amplification from aneuploidy and define the limits of amplification, we also observed co-amplification of the retinoic acid-alpha receptor with erbB2 and topoisomerase II alpha in the same three samples. At the topoisomerase I locus on chromosome 20, we observed allelic loss in two out of 17 samples. Genetics abberations at topoisomerase loci, therefore, appear to be relatively common in breast cancer.