The first patients treated with MR-CBCT soft-tissue matching in a MR-only prostate radiotherapy pathway.

INTRODUCTION: Magnetic Resonance (MR)-only radiotherapy for prostate cancer has previously been reported using fiducial markers for on-treatment verification. MR-Cone Beam Computed Tomography (CBCT) soft-tissue matching does not require invasive fiducial markers and enables MR-only treatments to other pelvic cancers. This study evaluated the first clinical implementation of MR-only prostate radiotherapy using MR-CBCT soft-tissue matching. METHODS: Twenty prostate patients were treated with MR-only radiotherapy using a synthetic (s)CT-optimised plan with MR-CBCT soft-tissue matching. Two MR sequences were acquired: small Field Of View (FOV) for target delineation and large FOV for organs at risk delineation, sCT generation and on-treatment verification. Patients also received a CT for validation. The prostate was independently contoured on the small FOV MR, copied to the registered CT and modified if there were MR-CT soft-tissue alignment differences (MR-CT volume). This was compared to the MR-only volume with a paired t-test. The treatment plan was recalculated on CT and the doses compared. Independent offline CT-CBCT matches for 5/20 fractions were performed by three therapeutic radiographers using the MR-only contours and compared to the online MR-CBCT matches using two one-sided paired t-tests for equivalence within ±1 mm. RESULTS: The MR-only volumes were significantly smaller than MR-CT (p = 0.003), with a volume ratio 0.92 ± 0.02 (mean ± standard error). The sCT isocentre dose difference to CT was 0.2 ± 0.1%. MR-CBCT soft-tissue matching was equivalent to CT-CBCT (p < 0.001), with differences of 0.1 ± 0.2 mm (vertical), -0.1 ± 0.2 mm (longitudinal) and 0.0 ± 0.1 mm (lateral). CONCLUSIONS: MR-only radiotherapy with soft-tissue matching has been successfully clinically implemented. It produced significantly smaller target volumes with high dosimetric and on-treatment matching accuracy. IMPLICATIONS FOR PRACTICE: MR-only prostate radiotherapy can be safely delivered without using invasive fiducial markers. This enables MR-only radiotherapy to be extended to other pelvic cancers where fiducial markers cannot be used.

Comparison of a simple dose-guided intervention technique for prostate radiotherapy with existing anatomical image guidance methods.

OBJECTIVES: A simple dose-guided intervention technique for prostate radiotherapy using an isodose overlay method combined with soft-tissue-based corrective couch shifts has been proposed previously. This planning study assesses the potential clinical impact of such a correction strategy. METHODS: 10 patients, each with 8-11 on-treatment CT studies (n=97), were assessed using this technique and compared with no intervention, bony anatomy intervention and soft-tissue intervention methods. Each assessment technique used a 4-mm action level for intervention. Outcomes were evaluated using measures of sensitivity, specificity and dosimetric effect, and compared across intervention techniques. Dosimetric effect was defined as the change in dosimetric coverage by the 95% isodose from the no intervention case of an evaluation construct called the verification target volume. RESULTS: Bony anatomy, soft tissue and dosimetric overlay-based interventions demonstrated sensitivity of 0.56, 0.73 and 1.00 and specificity of 0.64, 0.20 and 0.66, respectively. A detrimental dosimetric effect was shown in 7% of interventions for each technique, with benefit in 30%, 35% and 55% for bony anatomy, soft tissue and dosimetric overlay techniques, respectively. CONCLUSION: Used in conjunction with soft-tissue-based corrective couch shifts, the dosimetric overlay technique allows effective filtering out of dosimetrically unnecessary interventions, making it more likely that any intervention made will result in improved target volume coverage.

A dose distribution overlay technique for image guidance during prostate radiotherapy.

Adaptive radiotherapy involves altering the treatment plan according to variations in patient anatomy and set-up. This relies upon an accurate representation of the changing dose distribution within the patient, requiring a full dose recalculation. This work proposes a novel workflow using the planned dose distribution to assess dose coverage in three-dimensional verification CT studies acquired at the time of treatment delivery, using an overlay technique, in lieu of a recalculated dose distribution. The concept has been validated in a pilot study of 10 patients, each with 7-10 on-treatment CT studies. Differences between the geometric shape of the treatment plans for the 95% isodose and the 95% isodose obtained when the planned geometry was recalculated from the verification CT dataset were quantified. Dosimetric coverage of the verification clinical target volume (vCTV) was assessed for both the proposed overlay technique and the recalculated "delivered" dose distribution, and the conclusions on adequacy were compared. Results were consistent with geometric uncertainties of the dose calculation matrix (5 x 5 x 5 mm), suggesting that differences in the geometric shape of the 95% isodose are not significant for normal variations in patients' anatomy. Decisions on adequacy of vCTV coverage were consistent in 80 out of 87 cases, with discrepancies limited to a maximum of three axial slices per study within the range 0.5-4.5 mm (mean, 1.6 mm). The proposed dosimetric overlay technique has been validated and found to be an acceptable method of image-guided radiotherapy of the prostate suitable for effective implementation in the treatment clinic.

Dosimetric and treatment planning considerations for radiotherapy of the chest wall.

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.

Paediatric pelvic imaging: optimisation of dose and technique using digital grid-controlled pulsed fluoroscopy.

BACKGROUND: An audit of paediatric pelvic radiographs identified deficiencies in gonad shield placement and radiographic technique. OBJECTIVE: A technique using grid-controlled fluoroscopy (GCF), with hard copy images in frame grab and digital spot image (DSI) format was evaluated to optimise gonad shield placement and reduce the dose given to children with Perthes disease and Developmental Hip Dysplasia (DDH) attending for pelvic radiography. MATERIALS AND METHODS: Phantom and patient dose surveys of conventional and fluoroscopic techniques were carried out. Image quality and radiation dose were compared for the frame grab and DSI techniques. Retrospective evaluation was undertaken to compare their clinical acceptability. RESULTS: Both fluoroscopic techniques gave considerably less radiation than conventional non-grid radiography (67-83%, P < 0.05). The frame grab technique gave less radiation than DSI (P < 0.05). There was no significant difference in the clinical acceptability scores of the DSI and frame grab images. CONCLUSION: Fluoroscopy acquired images are now used since the fluoroscopic techniques give much less dose than conventional radiography and provide images of sufficient quality for clinical assessment. Indeed, as there was no significant difference in clinical usefulness between the frame grab and DSI techniques, it is planned to use frame grab alone, thus gaining additional dose saving.

Long-term culture of primary breast cancer in defined medium.

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.

Co-amplification of erbB2, topoisomerase II alpha and retinoic acid receptor alpha genes in breast cancer and allelic loss at topoisomerase I on chromosome 20.

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.

An evaluation of radiofrequency exposure from therapeutic diathermy equipment in the light of current recommendations.

Shortwave and microwave diathermy equipment use by physiotherapy departments in Grampian Region has been studied. Stray electric and magnetic fields close to equipment have been measured and compared with exposure levels recommended by the INIRC and the NRPB. Fields above the recommended whole body levels extend to 0.5-1.0 m from the electrodes and cables for continuous wave (cw) shortwave equipment, and up to 0.5 m for microwave units and pulsed shortwave models. Operators were exposed to local fields above these values for 2 - 3 min during cw shortwave treatments, but rarely exceeded the recommended exposure. However, short localised exposures to high fields, which can occur if the operator moves close to the electrodes or cables, could exceed these limits. Physiotherapists are advised to remain at a distance of at least 1 m during cw treatments, and not to approach within 0.5 m of the electrodes and cables even for a short period.

Occult primary seminoma: eighteen-year delay in presentation.

Primary retroperitoneal seminoma is well documented. A case is reported in which a patient presented with a seminoma of testis eighteen years after removal of a retroperitoneal seminoma. Histologic appearance of the testis was identified to the original pathology, and it is proposed that this represents recurrence of an occult testicular seminoma.

Lymphocytic infiltration of the prostate.

Symptomatic presentation due to lymphocytic infiltration of the prostate is rare. Six patients are described in whom lymphocytic infiltration of the prostate was secondary to non-Hodgkin's lymphoma, chronic lymphatic leukaemic, and myeloid leukaemia. The prostatic infiltration was sufficiently extensive to result in outflow tract obstruction.

Long-term effects of cold cardioplegic myocardial protection in the rat.

The long-term histologic effects of the use of two cold cardioplegic solutions (St. Thomas' and saline) were studied and compared in a model of heterotopic cardiac transplantation in rats of isogeneic strain. After cold cardioplegic arrest, hearts were stored for varying times ("minimal," 30, or 90 minutes) in one of the solution prior to transplantation, giving a total of six groups (five animals in each group). Early assessment of myocardial injury 48 hours after transplantation was by the uptake of technetium 99m pyrophosphate and by measurement of serum creatine kinase activity. Late assessment of myocardial injury at 3 months after transplantation was by quantitative histologic examination. The findings indicated that significant myocardial fibrosis occurred in hearts stored in both solutions for the longest storage period (90 minutes) and that St. Thomas' cardioplegic formula conferred better myocardial protection after 90 minutes' storage than did cold saline, as judged by the degree of histologic injury at 3 months (p less than 0.025). Significant correlation was found between long-term histologic changes at 3 months and the uptake of technetium 99m pyrophosphate (p less than 0.001) and serum creatine kinase activity (p less than 0.05) assessed at 48 hours. Uptake of technetium 99m pyrophosphate and increased serum creatine kinase activity was demonstrated 48 hours after injury in animals having no detectable histologic injury at 3 months. These observations indicate that there may be technetium 99m pyrophosphate uptake and enzyme release from reversibly damaged myocardial cells.