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D P Dearnaley

Publications and source records attributed to D P Dearnaley.

At least 55 records · Page 3Linked to original sources
PubMed2001

Relationship between glutathione S-transferase M1, P1 and T1 polymorphisms and early onset prostate cancer.

There is evidence suggesting that polymorphic variations in the glutathione S-transferases (GSTs) are associated with cancer susceptibility. Inter-individual differences in cancer susceptibility may be mediated in part through polymorphic variability in the bioactivation and detoxification of carcinogens. The GSTs have been consistently implicated as cancer susceptibility genes in this context. The GST supergene family includes several loci with well characterized polymorphisms. Approximately 50% of the Caucasian population are homozygous for deletions in GSTM1 and approximately 20% are homozygous for deletions in GSTT1, resulting in conjugation deficiency of mutagenic electrophiles to glutathione. The GSTP1 gene has a polymorphism at codon 105 resulting in an Ile to Val substitution which consequently alters the enzymatic activity of the protein and this has been suggested as a putative high-risk genotype in various cancers. We investigated the relationship between GST polymorphisms and young onset prostate cancer in a case-control study. GSTM1, GSTT1 and GSTP1 genotypes were determined for 275 prostate cancer patients and for 280 geographically matched control subjects. We found no significant difference in the frequency of GSTM1 or GSTT1 null genotypes between cases and controls. GSTP1 genotype was, however, significantly associated with prostate cancer risk: the Ile/Ile homozygotes had the lowest risk and there was a trend in increasing the risk with the number of 105 Val alleles: Ile/Val odds ratio (OR)= 1.30 (95% FCI 0.99-1.69), Val/Val OR = 1.80 (95% FCI 1.11-2.91); Ptrend = 0.026. These results suggest that the GSTP1 polymorphism may be a risk factor for developing young onset prostate cancer. We also found that carrying more than one putative high-risk allele in the carcinogen metabolizing GST family was associated with an elevated risk for early onset prostate cancer (OR 2.48, 95% FCI 1.22-5.04, Ptrend = 0.017).

Adult↗
PubMed2001

Effects of androgen deprivation on prostatic morphology and vascular permeability evaluated with mr imaging.

PURPOSE: To assess magnetic resonance (MR) measures of vascular permeability of prostate cancer treated with androgen deprivation and to correlate these with morphologic appearances and serum prostate-specific antigen (PSA) levels. MATERIALS AND METHODS: MR examinations in 56 consecutive patients with prostate cancer were performed before and after luteinizing hormone-releasing hormone analog treatment. T2-weighted and contrast medium-enhanced T1-weighted MR images were obtained. Pre- and posttreatment comparisons of morphologic features, glandular volume, and enhancement-related parameters (capillary permeability, leakage space, gadolinium accumulation) were made. RESULTS: Fifty-five tumors were seen before treatment; 42, after treatment. Signal intensity in the peripheral zone and seminal vesicles decreased on T2-weighted images in 42 (75%) and 25 (45%) patients, respectively. Median volume in tumor decreased by 65% (95% CI: 55%, 76%); in central gland, by 30% (95% CI: 25%, 35%). Reductions in tumor permeability (P <.001) and changes in washout patterns were observed (P <.001). Tumor permeability reductions coincided with a decrease in serum PSA levels in 91% of patients. A weak correlation between tumor permeability and volume change was seen (r = 0.55, P =.04). Reductions in peripheral zone (P <.001) and central gland (P =.009) permeability were noted. CONCLUSION: Androgen deprivation decreases tumor volume and vascular permeability and impairs detection of prostate cancers. Use of MR estimates of permeability may be an additional way of assessing prostatic tumor response to antiandrogen treatment.

Aged↗
PubMed2001

Evaluation of the optimal co-planar field arrangement for use in the boost phase of dose escalated conformal radiotherapy for localized prostate cancer.

The aim of this study was to determine the optimal co-planar beam arrangement from a variety of three-field (3F), four-field (4F) and six-field (6F) plans for the boost phase of a dose escalated conformal radiotherapy schedule. Three selected plans (3F 0 degrees, 90 degrees, 270 degrees plan, 4F 45 degrees, 90 degrees, 270 degrees, 315 degrees plan and 6F 40 degrees, 90 degrees, 115 degrees, 245 degrees, 270 degrees, 320 degrees plan) were compared with reference plans (3F 0 degrees, 120 degrees, 240 degrees plan, 4F 0 degrees, 90 degrees, 180 degrees, 270 degrees plan, 6F 55 degrees, 90 degrees, 125 degrees, 235 degrees, 270 degrees, 305 degrees plan and 6F 50 degrees, 90 degrees, 130 degrees, 230 degrees, 270 degrees, 310 degrees plan) in 10 patients. Doses of 64 Gy and 74 Gy were prescribed to the isocentre using 6 MV photons. The boost planning target volume comprised the prostate gland alone without a margin. Plans were compared by means of rectal volumes irradiated to >50% (V50), >80% (V80) and >90% (V90) of the prescribed dose. Irradiated volumes were also measured for the bladder (V90) and the femoral heads (V70). All optimal 3F, 4F and 6F plans gave lower irradiated rectal V80 and V90 levels than their corresponding reference plan. The 3F (0 degrees, 90 degrees, 270 degrees) plan consistently provided lower irradiated rectal levels at V50 to V90, with acceptable bladder and femoral head doses compared with the other plans in the study. When the 6F (50 degrees, 90 degrees, 130 degrees, 230 degrees, 270 degrees, 310 degrees) plan used at our institution for the boost phase was compared with the 3F (0 degrees, 90 degrees, 270 degrees) plan, the rectal V50 was reduced from 20.8+/-5.2%, to 12.6+/-5.1%, the rectal V80 was reduced from 8.7+/-2.9% to 6.5+/-3.1% and the rectal V90 was reduced from 5.5+/-2.1% to 3.9+/-2.0% (all p<0.001). The bladder V90 and the femoral heads V70 levels were equivalent. For the boost phase when escalating the dose from 64 Gy to 74 Gy, the co-planar plan that allowed optimal rectal sparing was a 3F beam arrangement using gantry angles of 0 degrees, 90 degrees and 270 degrees. This 3F plan provided improved rectal sparing compared with the 6F (50 degrees, 90 degrees, 130 degrees, 230 degrees, 270 degrees, 310 degrees) beam arrangement currently used at our institution, with equivalent and acceptable bladder and femoral head doses.

Aged↗
PubMed2000

Reduction of small and large bowel irradiation using an optimized intensity-modulated pelvic radiotherapy technique in patients with prostate cancer.

PURPOSE: To investigate the role of intensity-modulated radiation therapy (IMRT) to irradiate the prostate gland and pelvic lymph nodes while sparing critical pelvic organs, and to optimize the number of beams required. METHODS AND MATERIALS: Target, small bowel, colon, rectum, and bladder were outlined on CT planning scans of 10 men with prostate cancer. Optimized conventional (RT) and 3-dimensional conformal radiotherapy (3D-CRT) plans were created and compared to inverse-planned IMRT dose distributions using dose-volume histograms. Optimization of beam number was undertaken for the IMRT plans. RESULTS: With RT the mean percentage volume of small bowel and colon receiving >45 Gy was 21.4 +/- 5.4%. For 3D-CRT it was 18.3 +/- 7.7% (p = 0.0043) and for 9-field IMRT it was 5.3 +/- 1.8% (p < 0.001 compared to 3D-CRT). For 7, 5, and 3 IMRT fields, it was 6.4 +/- 2.9%, 7.2 +/- 2.8%, and 8.4 +/- 3.8% (all p < 0.001 compared to 3D-CRT). The rectal volume irradiated >45 Gy was reduced from 50.5 +/- 16.3% (3D-CRT) to 5.8 +/- 2.1% by 9-field IMRT (p < 0. 001) and bladder from 52.2 +/- 12.8% to 7 +/- 2.8% (p < 0.001). Similar benefits were maintained for 7, 5, and 3 IMRT fields. CONCLUSIONS: The reduction in critical pelvic organ irradiation seen with IMRT may reduce side effects in patients, and allow modest dose escalation within acceptable complication rates. These reductions were maintained with 3-5 IMRT field plans which potentially allow less complex delivery techniques and shorter delivery times.

Colon↗
PubMed2000

The frequency of germ-line mutations in the breast cancer predisposition genes BRCA1 and BRCA2 in familial prostate cancer. The Cancer Research Campaign/British Prostate Group United Kingdom Familial Prostate Cancer Study Collaborators.

Predisposition to prostate cancer has a genetic component, and there are reports of familial clustering of breast and prostate cancer. Two highly penetrant genes that predispose individuals to breast cancer (BRCA1 and BRCA2) are known to confer an increased risk of prostate cancer of about 3-fold and 7-fold, respectively, in breast cancer families. Blood DNA from affected individuals in 38 prostate cancer clusters was analyzed for germ-line mutations in BRCA1 and BRCA2 to assess the contribution of each of these genes to familial prostate cancer. Seventeen DNA samples were each from an affected individual in families with three or more cases of prostate cancer at any age; 20 samples were from one of affected sibling pairs where one was < or = 67 years at diagnosis. No germ-line mutations were found in BRCA1. Two germ-line mutations in BRCA2 were found, and both were seen in individuals whose age at diagnosis was very young (< or = 56 years) and who were members of an affected sibling pair. One is a 4-bp deletion at base 6710 (exon 11) in a man who had prostate cancer at 54 years, and the other is a 2-bp deletion at base 5531 (exon 11) in a man who had prostate cancer at 56 years. In both cases, the wild-type allele was lost in the patient's prostate tumor at the BRCA2 locus. However, intriguingly, in neither case did the affected brother also carry the mutation. Germ-line mutations in BRCA2 may therefore account for about 5% of prostate cancer in familial clusters.

Adult↗
PubMed2000

Optimization of coplanar six-field techniques for conformal radiotherapy of the prostate.

PURPOSE: To determine the optimal coplanar treatment technique for six-field conformal radiotherapy of prostate only (PO) or prostate plus seminal vesicles (PSV). METHODS AND MATERIALS: A series of 6-MV six-field coplanar treatment plans were created for PO and PSV volumes in 10 patients prescribed to both 64 and 74 Gy. All plans consisted of laterally-symmetric anterior oblique, lateral, and posterior oblique fields. The posterior oblique fields were varied through 20-45 degrees relative to the lateral fields, and for each of these angles, the anterior oblique fields were varied through 25-65 degrees relative to lateral. The plans were compared by means of rectal volumes irradiated to 80% or more of the prescribed dose (V80); normal tissue complication probability (NTCP) for rectum, bladder, and femoral heads; and tumor control probability (TCP). Femoral head tolerance was designated as 52 Gy to no more than 10% volume. RESULTS: For the PO group, anterior oblique fields at 50 degrees from lateral and posterior oblique fields at 25 degrees from lateral produced the lowest V80, together with femoral head doses which were appropriate for most patients (V80 = 24.4+/-5.3% [1 SD]). Compared to a commonly-used six-field (reference) plan with both anterior and posterior oblique fields at 35 degrees from lateral (V80 = 26.3+/-5.9%), this represented an improvement (p = 0.001). For the PSV group, the optimal anterior and posterior oblique fields were at 65 degrees and 30 degrees from lateral, respectively (V80 = 47.5+/-6.3%). Relative to the reference plan (V80 = 49.4+/-5.6%), this was a marginal improvement (p = 0.07). CONCLUSION: The optimized six-field plans provide increased rectal sparing at both standard and escalated doses. Moreover, the gain in TCP resulting from dose escalation can be achieved with a smaller increase in rectal NTCP using the optimized six-field plans.

Aged↗
PubMed2000

An evaluation of three-field coplanar plans for conformal radiotherapy of prostate cancer.

BACKGROUND AND PURPOSE: A series of coplanar three-field configurations for two different clinical treatment volumes, prostate only (PO) and prostate plus seminal vesicles (PSV) were studied to determine the optimal three-field plan arrangement for prostate radiotherapy. MATERIALS AND METHODS: A variety of conformal three-field 6 MV plans prescribed to both 64 and 74 Gy were created for PO and PSV volumes in each of ten patients. For description, the orientation of each sequential beam was named in a clockwise fashion. Plans included series with arrangements of 0 degrees, 60-150 degrees, 210-300 degrees; 0 degrees, 90 degrees, 225-255 degrees; 90 degrees, 210-240 degrees, 300-330 degrees and a four-field (4F) box plan for comparison. Six-hundred and eighty plans were compared using the rectal volume irradiated to greater than 50% (V(50)), 80% (V(80)), and 90% (V(90)) of the prescribed dose, normal tissue complications (NTCP) for rectum, bladder, and femoral heads (FH), and tumour control probabilities (TCP). FH tolerance was set at 52 Gy to 10% volume. RESULTS: In comparing the 34 different three-field configurations for each of the PO and PSV groups, the greatest rectal sparing was achieved by a three-field plan with gantry angles of 0 degrees, 90 degrees, 270 degrees (PO: rectal V(80)=22.8+/-5.5% (1S.D.), V(90)=18.4+/-5.7%, and PSV: rectal V(80)=41.9+/-5.8%, V(90)=35.5+/-5.9%). This also improved on the 4F-box plan (PO: rectal V(80)=26.0+/-5.8%, V(90)=21.4+/-5.2%, P<0.001; and PSV: rectal V(80)=47.3+/-5.5%, V(90)=41.6+/-5.1%, P<0.001). The worst rectal sparing was seen with the 0 degrees, 120 degrees, 240 degrees plan (PO: rectal V(80)=35.2+/-8.0%, V(90)=30.3+/-7.1%, P<0.001; and PSV: rectal V(80)=65.7+/-9.0%, V(90)=58.8+/-8.8%, P<0.001). In the PO group, the increase in predicted rectal NTCP with dose escalation from 64 to 74 Gy was 3.3% using the 0 degrees, 90 degrees, 270 degrees plan, 4.7% with the 4F-box plan, and 6.9% with the 0 degrees, 120 degrees, 240 degrees plan. In the PSV group, dose escalation increased the predicted rectal NTCP by 7.9, 10.1 and 15.7% for the 0 degrees, 90 degrees, 270 degrees plan, 4F-box plan, and 0 degrees, 120 degrees, 240 degrees plan, respectively. CONCLUSIONS: For both PO and PSV volumes, the three-field plan which afforded the greatest rectal sparing with acceptable bladder and femoral head doses was the 0 degrees, 90 degrees, 270 degrees plan. This plan also improved on the 4F-box. The increase in predicted rectal NTCP when escalating dose from 64 to 74 Gy was smaller using this plan compared to either the three-field 0 degrees, 120 degrees, 240 degrees plan or the 4F-box plan.

Aged↗
PubMed2000

A randomized study of the use of a customized immobilization system in the treatment of prostate cancer with conformal radiotherapy.

PURPOSE: To evaluate the impact of a customized immobilisation system on field placement accuracy, simulation and treatment delivery time, radiographer convenience and patient acceptability. PATIENTS AND METHODS: Thirty men receiving radical radiotherapy for prostate cancer were randomised using a cross over trial design to have radiotherapy planning and treatment given either in a conventional treatment position (CTP) or using an immobilisation system (IMS). The randomisation was to have either the CTP or IMS for the initial 3 weeks of radiotherapy after which patients were replanned and changed to the alternative treatment set-up. Treatment accuracy was measured using an electronic portal imaging device. Radiographers and patients completed weekly questionnaires. RESULTS: Median simulation time was 22.5 min (range 20-30 min) in the CTP and 25 min (range 15-40 min) for the IMS (P < 0.001). Median treatment time was 9 min for CTP (range 8-10 min), and 10 min (range 8.5-13.5 min) for IMS (P < 0.001). Median isocentre displacement for anterior fields was 1.7 mm from the simulated isocentre for the CTP compared to 2.0 mm for IMS (P = 0.07). For left lateral fields values were 1.8 and 1.8 mm (P = 0.98), and for right lateral fields 2.1 and 1.7 mm (P = 0.06), respectively. No clinically significant reduction in either systematic or random field placement errors was demonstrated. Radiographers reported that patients found the IMS more comfortable than CTP (P < 0.001), but when using the IMS, they noticed greater difficulty in patient positioning (P < 0.001), and alignment to skin tattoos (P < 0.001). CONCLUSIONS: Although IMS may have been more comfortable, treatment accuracy was not improved compared to the CTP in our department. In addition, treatment took longer and patient set-up was more difficult.

Aged↗
PubMed2000

Abdominal relapse in stage 1 nonseminomatous germ cell tumours of the testis managed by surveillance or with adjuvant chemotherapy.

OBJECTIVE: To assess the impact on patterns of recurrence of adjuvant chemotherapy in patients with stage 1 nonseminomatous germ cell tumours (NSGCT) of the testis, who have a high likelihood of relapse on surveillance if certain risk factors are identified in the orchidectomy specimen, and thus the theoretical need for retroperitoneal lymph node dissection (RPLND). PATIENTS AND METHODS: The incidence of abdominal relapse was recorded in 417 men presenting with stage 1 NSGCT over the past 18 years. Up to 1986, 161 men were managed by surveillance alone, and abdominal relapse occurred in 26. From 1986 onwards, men with positive risk factors in the orchidectomy specimen were offered two courses of chemotherapy; 60 accepted and one relapsed in the abdomen, and 196 underwent surveillance and 19 relapsed in the abdomen. RESULTS: Abdominal relapse was significantly reduced from 16% before 1986 to 8% afterward (P = 0.014). Mortality from testicular tumour or treatment toxicity remained low, at 0.6% before 1986 and 2.0% since then. CONCLUSION: The need for RPLND in stage 1 NSGCT remains highly doubtful.

Abdominal Neoplasms↗
PubMed2000

Dynamic contrast enhanced MRI of prostate cancer: correlation with morphology and tumour stage, histological grade and PSA.

AIM: To quantify MRI enhancement characteristics of normal and abnormal prostatic tissues and to correlate these with tumour stage, histological grade and tumour markers. MATERIALS AND METHODS: Quantitative gradient recalled echo MR images were obtained following bolus injection of gadopentetate dimeglumine in 48 patients with prostate cancer. Turbo spin-echo T2-weighted images at the same anatomical position were reviewed for the presence of tumours (45 regions), normal peripheral zone (33 regions), and normal appearing central gland (30 regions). Time-signal intensity parameters (onset time, mean gradient and maximal amplitude of enhancement and wash-out score) and modelling parameters (permeability surface area product, lesion leakage space and maximum gadolinium concentration) were correlated with tumour stage, histological grade (Gleason score) and serum prostatic specific antigen (PSA) levels. RESULTS: Significant differences were noted between peripheral zone and tumour with respect to signal intensity and modelling parameters (P = 0.0001), except onset time. No differences between central gland and tumour enhancement values were seen. There was weak correlation between MRI tumour stage and tumour vascular permeability (r(2) = 12%; P = 0.02) and maximum tumour gadolinium concentration (r(2) = 14%; P = 0.015). However, no significant correlations were seen with Gleason score or PSA levels. CONCLUSION: Quantification of MR contrast enhancement characteristics allows tissue discrimination in prostate cancer consistent with known variations in microvessel density estimates.

Aged↗
PubMed2000

The utility of tumour markers in assessing the response to chemotherapy in advanced bladder cancer.

In patients with advanced bladder cancer receiving chemotherapy, early assessment of response can avoid unnecessary toxicity. The aim of this study was to assess the role of tumour markers in monitoring response. Serum levels of one or more of markers beta human chorionic gonadotrophin (betahCG), carcinoembryomic antigen (CEA), CA125 and CA19.9 were measured in 74 patients with advanced bladder cancer receiving chemotherapy from 1992 to 1997. Forty-three of 74 (58%) of patients had at least one raised marker (1.5 times upper limit of normal range). This was more common in patients with extra-pelvic disease than in those with disease confined to the pelvis (P = 0.002). Thirty-eight of 78 (49%) assessable patients had a radiological response. Neither clinical response (P = 0.81) nor survival (P = 0.16) differed between marker-negative and marker-positive patients. Clinical response was strongly related to marker response in the 35 comparable patients (P = 0.0001). No patient had a clinical response without response of at least one marker. Ninety per cent of patients who achieved a marker response had done so by 8 weeks. Monitoring of tumour markers in patients with advanced bladder cancer can help predict the response to chemotherapy.

Adult↗
PubMed2000

A medical research council randomized trial of single agent carboplatin versus etoposide and cisplatin for advanced metastatic seminoma. MRC Testicular Tumour Working Party.

The UK Medical Research Council conducted this trial of carboplatin chemotherapy in advanced seminoma to compare single agent carboplatin with a standard combination of etoposide with cisplatin. The use of single agent carboplatin was expected to be associated with reduced toxicity. A total of 130 patients with advanced seminoma were randomly assigned to treatment with either single agent carboplatin (C) at a dose of 400 mg/m(2)to be corrected for glomerular filtration rate outside the range 81-120 ml min(-1)and to be administered on day 1 of a 21 day cycle to a total of 4 cycles or to etoposide + platinum (EP). The trial was designed as an equivalence study aiming to exclude a reduction in the 3-year progression-free survival in patients allocated to carboplatin of between 10 and 15%, requiring initially a target accrual of 250 patients (90% power significance level 5% (one-sided)). The trial closed after 130 patients had been randomized following recommendation by an independent data monitoring committee. At a median follow-up time of 4.5 years, 81% of patients had been followed up for at least 3 years and 19 patients have died. The estimated PFS rate (95% Confidence Intervals (CI)) at 3 years was 71% (60-82%) in patients allocated C and 81% (71-90%) in those allocated EP; the 95% CI for the difference in 3 year PFS was - 6% to +19%. The hazard ratio of 0.64 (95% CI 0.32-1.28) favoured EP but the difference was not statistically significant (log rank chi-squared = 1.59 P = 0.21). The 3-year survival rate was 84% (75-92%) in those allocated C, and 89% (81-96%) in those allocated EP. The hazard ratio for survival was 0.85 with 95% CI, 0.35-2.10, log rank chi-squared = 0.12, P = 0.73. The trial has not demonstrated statistically significant differences in the major survival endpoints comparing single agent carboplatin with a combination of etoposide + cisplatin. This cannot be taken as an indication of equivalence since the limited size of this trial rendered it unable to exclude a 19% lower progression-free survival and survival in those treated with single agent carboplatin which would be important clinically. Standard initial chemotherapy for advanced seminoma should be based on cisplatin combinations and the role of carboplatin awaits the outcome of further studies.

Antineoplastic Agents↗
PubMed2000

Radiotherapy planning of the pelvis using distortion corrected MR images: the removal of system distortions.

Image distortion is an important consideration in the use of magnetic resonance (MR) images for radiotherapy planning. The distortion is a consequence of system distortion (arising from main magnetic field inhomogeneity and nonlinearities in the applied magnetic field gradients) and of effects arising from the object/patient being imaged. A two stage protocol has been developed to correct both system and object-induced distortion in pelvic images which incorporates measures to maintain the quality, accuracy and consistency of the imaging and correction procedures. The first stage of the correction procedure is described here and involves the removal of system distortion. Object- (patient-) induced effects will be described in a subsequent work. Images are acquired with the patient lying on a flat rigid bed, which reproduces treatment conditions. A frame of marker tubes surrounding the patient and attached to the bed provides quality assurance data in each image. System distortions in the three orthogonal planes are mapped using a separate phantom, which fits closely within the quality control frame. Software has been written which automates the measurement and checking of the many marker positions which the test objects generate and which ensures that patient data are acquired using a consistent imaging protocol. Results are presented which show that the scanner and the phantoms used in measuring distortion give highly reproducible results with mean changes of the order of 0.1 mm between repeated measurements of marker positions in the same imaging session. Effective correction for in plane components of system distortion is demonstrated.

Humans↗
PubMed2000

Intensity modulated radiation therapy: a clinical review.

Intensity modulated radiotherapy represents a significant advance in conformal radiotherapy. In particular, it allows the delivery of dose distributions with concave isodose profiles such that radiosensitive normal tissue close to, or even within a concavity of, a tumour may be spared from radiation injury. This article reviews the clinical application of this technique to date, and discusses the practical issues of treatment planning and delivery from the clinician's perspective.

Algorithms↗
PubMed1999

Androgen receptor polymorphisms: association with prostate cancer risk, relapse and overall survival.

Several reports have suggested that one or both of the trinucleotide repeat polymorphisms in the human androgen receptor (hAR) gene, (CAG)n coding for polyglutamine and (GGC)n coding for polyglycine, may be associated with prostate cancer risk; but no study has investigated their association with disease progression. We present here a study of both hAR trinucleotide repeat polymorphisms not only as they relate to the initial diagnosis but also as they are associated with disease progression after therapy. Lymphocyte DNA samples from 178 British Caucasian prostate cancer patients and 195 control individuals were genotyped by PCR for the (CAG)n and (GGC)n polymorphisms in hAR. Univariate Cox proportional hazard analysis indicated that stage, grade and GGC repeat length were individually significant factors associated with disease-free survival (DFS) and overall survival (OS). The relative risk (RR) of relapse for men with more than 16 GGC repeats was 1.74 (95% CI 1. 08-2.79) and of dying from any cause, 1.98 (1.13-3.45). Adjusting for stage and grade, GGC effects remained but were not significant (RR(DFS)= 1.60, p = 0.052; RR(OS)= 1.65, p = 0.088). The greatest effects were in stage T1-T2 (RR(DFS)= 3.56, 95% CI 1.13-11.21) and grade 1 (RR(DFS)= 6.47, 95% CI 0.57-72.8) tumours. No differences between patient and control allele distributions were found by odds-ratio analysis, nor were trends with stage or grade evident in the proportion of short CAG alleles. Non-significant trends with stage and grade were found in the proportion of short GGC alleles. The (GGC)n polymorphism in this population is a significant predictor of disease outcome. Since the (GGC)(n) effect is strongest in early-stage tumours, this marker may help forecast aggressive behaviour and could be used to identify those patients meriting more radical treatment.

Aged↗
PubMed1999

Evaluating the effect of rectal distension and rectal movement on prostate gland position using cine MRI.

PURPOSE: To evaluate the dynamic interrelationship between rectal distension and rectal movements, and to determine the effect of rectal movement on the position of the prostatic gland using cine magnetic resonance imaging (MRI). METHODS AND MATERIALS: Fifty-five patients with biopsy-proven or suspected prostate cancer were examined in the axial plane using repeated spoiled gradient-echo sequences every 10 seconds for 7 minutes. Twenty-four patients received bowel relaxants before imaging. Images were analyzed for the degree of rectal distension, for the incidence, magnitude, and number of rectal and prostate movements. RESULTS: Rectal movements were seen in 28 (51%) patients overall, in 10 (42%) of those receiving bowel relaxants and in 18 (58%) not receiving bowel relaxants. The incidence of rectal movements correlated with the degree of rectal distension (p = 0.0005), but the magnitude of rectal movements did not correlate with the degree of rectal distension. Eighty-six rectal movements resulting in 33 anterior-posterior (AP) prostate movements were seen. The magnitude of rectal movements correlated well with degree of prostate movements (p < 0.001). Prostate movements in the AP direction were seen in 16 (29%) patients, and in 9 (16%) patients the movement was greater than 5 mm. The median prostate AP displacement was anterior by 4.2 (-5 to +14 mm). CONCLUSIONS: Cine MRI is able to demonstrate near real time rectal and associated prostate movements. Rectal movements are related to rectal distension and result in significant displacements of the prostate gland over a time period similar to that used for daily fractionated radiotherapy treatments. Delivery of radiotherapy needs to take into account these organ movements.

Aged↗
PubMed1999

Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomised trial.

BACKGROUND: Radical radiotherapy is commonly used to treat localised prostate cancer. Late chronic side-effects limit the dose that can be given, and may be linked to the volume of normal tissues irradiated. Conformal radiotherapy allows a smaller amount of rectum and bladder to be treated, by shaping the high-dose volume to the prostate. We assessed the ability of this new technology to lessen the risk of radiation-related effects in a randomised controlled trial of conformal versus conventional radiotherapy. METHODS: We recruited men with prostate cancer for treatment with a standard dose of 64 Gy in daily 2 Gy fractions. The men were randomly assigned conformal or conventional radiotherapy treatment. The primary endpoint was the development of late radiation complications (> 3 months after treatment) measured with the Radiation Therapy and Oncology Group (RTOG) score. Indicators of disease (cancer) control were also recorded. FINDINGS: In the 225 men treated, significantly fewer men developed radiation-induced proctitis and bleeding in the conformal group than in the conventional group (37 vs 56% > or = RTOG grade 1, p=0.004; 5 vs 15% > or = RTOG grade 2, p=0.01). There were no differences between groups in bladder function after treatment (53 vs 59% > or = grade 1, p=0.34; 20 vs 23% > or = grade 2, p=0.61). After median follow-up of 3.6 years there was no significant difference between groups in local tumour control (conformal 78% [95% CI 66-86], conventional 83% [69-90]). INTERPRETATION: Conformal techniques significantly lowered the risk of late radiation-induced proctitis after radiotherapy for prostate cancer. Widespread introduction of these radiotherapy treatment methods is appropriate. Our results are the basis for dose-escalation studies to improve local tumour control.

Follow-Up Studies↗