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Biomedical subjects

R W Laing

Publications and source records attributed to R W Laing.

At least 19 recordsLinked to original sources
PubMed2006

Interstitial low dose rate brachytherapy for prostate cancer--a focus on intermediate- and high-risk disease.

AIMS: To investigate the role of brachytherapy in intermediate- and high-risk prostate cancer. We report our results and a review of published studies. MATERIALS AND METHODS: Between March 1999 and April 2003, 300 patients were treated with low dose rate 1-125 interstitial prostate brachytherapy and followed prospectively. The patients were stratified into low-, intermediate- and high-risk groups and received brachytherapy alone or in combination with external beam radiotherapy (EBRT) and/or neoadjuvant androgen deprivation (NAAD). One hundred and forty-six patients were classified as low risk, 111 as intermediate risk and 43 as high risk. Biochemical freedom from disease and prostate-specific antigen (PSA) nadirs were analysed for risk groups and for treatment received in each risk group. RESULTS: The median follow-up was 45 months (range 33-82 months) with a mean age of 63 years. Actuarial 5-year biochemical relapse-free survival for the low-risk group was 96%, 89% for the intermediate-risk group and 93% for the high-risk group. When stratified by treatment group, low-risk patients had a 5-year actuarial biochemical relapse-free survival of 94% for brachytherapy alone (n=77), 92% for NAAD and brachytherapy (n=66) and 100% for NAAD, EBRT and brachytherapy (n=3). In the intermediate-risk patients, biochemical relapse-free survival was 93% for brachytherapy alone (n=15), 94% for NAAD and brachytherapy (n=67), 75% for EBRT and brachytherapy (n=4) and 92% for NAAD, EBRT and brachytherapy (n=25). In the high-risk group, biochemical relapse-free survival was 100% for brachytherapy alone (n=2), 88% for NAAD and brachytherapy (n=7), 80% for EBRT and brachytherapy (n=5) and 96% for NAAD, EBRT and brachytherapy (n=29). Overall 3- and 4-year PSA = 0.5 ng/ml were achieved by 71 and 86%, respectively, and a 4-year PSA = 0.2 ng/ml was achieved by 63%. CONCLUSION: Although the role of combination treatment with pelvic EBRT and androgen therapy is not clear, our early results show that many patients with intermediate- and high-risk disease have excellent results with brachytherapy.

Adult↗
PubMed2005

Neoadjuvant vinorelbine/epirubicin (VE) versus standard adriamycin/cyclophosphamide (AC) in operable breast cancer: analysis of response and tolerability in a randomised phase III trial (TOPIC 2).

BACKGROUND: Vinorelbine is active and well tolerated against advanced breast cancer but there are no published efficacy studies in early breast cancer. We have therefore carried out a randomised phase III neoadjuvant trial in operable breast cancer. PATIENTS AND METHODS: Patients with > or =3 cm operable breast carcinoma were randomised to receive either vinorelbine 25 mg/m(2) on days 1 and 8 and epirubicin 60 mg/m(2) on day 1, 3 weekly for six cycles (VE) or doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) i.v. on day 1, 3 weekly for six cycles (AC), prior to standard local therapy, and adjuvant endocrine therapy as appropriate. RESULTS: A total of 451 patients were randomised. Results for AC and VE, respectively, were: overall clinical response 73% and 74%, complete clinical remission 20% and 24%, pathological complete remission 12% and 12%, mastectomy rate 52% and 55%. None of these differences were significant. Dose reduction was required in 8% for AC and 20% for VE (P <0.001) (GSCF support not used). Significantly more grade 3/4 toxicity for nausea, vomiting and alopecia (despite scalp cooling) was seen for AC compared with VE but significantly less grade 3/4 thrombophlebitis and neuropathy. CONCLUSIONS: Neoadjuvant VE is as effective as AC in early breast cancer and was better tolerated except for thrombophlebitis and neuropathy.

Adult↗
PubMed2005

Gleason scoring varies among pathologists and this affects clinical risk in patients with prostate cancer.

AIMS: To investigate whether our practice of specialist review of all diagnostic biopsies was necessary to prevent misgrading of referred prostate cancer patients, and whether this misclassification, if any, would have resulted in misclassification of clinical risk grouping (Seattle Risk Grouping [SRG]) and subsequent treatment strategy and prognosis. MATERIALS AND METHODS: Important prognostic indicators for prostate cancer include the presenting prostate-specific antigen (PSA), clinical stage and Gleason sum of the tumour. These three variables are incorporated into the SRG cohorts to establish treatment strategy. Patients with prostate cancer referred for brachytherapy had their prostate biopsies reviewed by a reference pathologist (PD) with a special interest in prostate cancer. We compared the agreement between the scoring of the referring pathologists with that of PD, and evaluated if any differences changed the SRG and therefore the clinical risk and treatment strategy for the patients. RESULTS: In only 52% (43/83) of cases, was there total agreement between the two sets of pathologists. The inter-rater agreement was statistically 'fair' (unweighted kappa statistic 0.27). In 90% (36/40) of cases with disagreement, PD assigned higher Gleason sums. In 40% (16/40) of cases with disagreement, the change in Gleason sum altered the SRG; in one out of 16 cases, the SRG was downgraded from 'intermediate' to 'low' risk disease; in six out of 16 cases, it was upgraded from 'low' to 'intermediate' risk, and, in nine out of 16, from 'intermediate' to 'high' risk. CONCLUSION: Our findings confirm previous reports of only limited correlation between pathologists in reporting Gleason sums. In this study, 19% (16/83) of cases had their grading changed to a level that altered clinical risk, almost always (94%; 15/16) to one that worsened prognosis. This would have significantly affected treatment strategy for these patients, and thus we recommend that all centres ensure accurate Gleason grading by the use of pathologists with special interests in prostate cancer.

Brachytherapy↗
PubMed2004

Toxicity and early biochemical outcomes from 125iodine prostate brachytherapy in the UK. A prospective study.

AIMS: Transperineal interstitial prostate brachytherapy is increasingly available to patients with early prostate cancer in the U.K., but limited data are available about the toxicity and early results in the U.K. prostate cancer population. We describe our experience and results from prostate brachytherapy to date. MATERIALS AND METHODS: Two hundred and fifty-five patients were treated at St Luke's Cancer Centre, Guildford, U.K., between March 1999 and November 2002. Of these, over 3 months of follow-up data were available for 216 patients. Patients were assessed at 6 weeks and then at 3, 6, 9 and 12 months after implant, and at 6 monthly intervals thereafter. Prostate-specific antigen (PSA), International Prostate Symptom Score (IPSS) and toxicity, including catheter use, was recorded prospectively. RESULTS: Median PSA at 1, 2 and 3 years was 0.5, 0.4 and 0.1 ng/ml, respectively. Ninety-five per cent of patients experienced temporary deterioration in their urinary symptoms, which persisted at clinically significant levels (IPSS increase >3 points) for 9 months after implant. The severity of urinary symptoms (IPSS) after implant was most closely related to IPSS at presentation (P<0.001). Acute urinary retention (AUR) occurred in 20 (9.3%) patients, with a further 26 (12.1%) patients using clean intermittent self-catheterisation (CISC) to reduce voiding frequency associated with chronic retention. Median duration of catheter use was 4 weeks. Multivariate analysis revealed that urodynamic status, prostate volume and IPSS score were independently significant (P<0.05) predictors of post-implant catheter use. Twelve patients (5.6%) reported either rectal urgency or mild, self-limiting rectal bleeding. CONCLUSION: Brachytherapy was tolerated well, with self-limiting urinary, bowel and sexual toxicity in most patients. Postoperative catheter use in our population is closely linked to pre-implant IPSS score, baseline prostate volume and urodynamic obstruction status. This work confirms the prognostic value of urodynamic assessment, which adds useful prognostic information to assessment of known risk factors such as prostate volume and IPSS.

Aged↗
PubMed2004

Iodine seed prostate brachytherapy: an alternative first-line choice for early prostate cancer.

This article on permanent iodine-125 seed prostate brachytherapy reviews the techniques, results, and patient selection issues for early prostate cancer. The long-term 10 y results of brachytherapy from Seattle, and their reproducibility in other centres both in the USA and UK are reported. The use of hormone therapy in brachytherapy and the value of combining external beam radiotherapy with a brachytherapy implant are discussed. Reviewed comparative data show the similarity of biochemical survival in patients treated with brachytherapy, radical prostatectomy, and external beam radiotherapy. The role of brachytherapy as a first-line treatment option for patients with prostate cancer is demonstrated.

Brachytherapy↗
PubMed2004

A novel continuous infusional 5-fluorouracil-based chemotherapy regimen compared with conventional chemotherapy in the neo-adjuvant treatment of early breast cancer: 5 year results of the TOPIC trial.

BACKGROUND: To compare the efficacy of continuous infusional 5-fluorouracil (5-FU)-based chemotherapy against conventional bolus chemotherapy in the preoperative treatment of patients with large operable early breast cancer. PATIENTS AND METHODS: Four hundred and twenty-six women with histologically proven 3 cm invasive early breast cancer were randomised to receive pre-operative infusional 5-FU 200 mg/m(2) by daily 24 h continuous infusion via a Hickman line for 18 weeks with epirubicin 60 mg/m(2) intravenous (i.v.) bolus on day 1 and cisplatin 60 mg/m(2) i.v. bolus on day 1, both repeating 3-weekly (infusional ECisF), or conventional bolus doxorubicin 60 mg/m(2) i.v. on day 1 and cyclophosphamide 600 mg/m(2) i.v. on day 1, both repeating 3-weekly (AC), both schedules for six courses. Patients subsequently had local therapy (surgery or radiotherapy or both) and tamoxifen 20 mg orally daily as appropriate. RESULTS: The 5 year results for AC and infusional ECisF, respectively, were as follows: overall response, 75% and 77%; complete clinical remission, 31% and 34%; pathological complete remission (pathCR), 16% for both; and pathCR with residual ductal carcinoma in situ (DCIS), 25% and 24%. Mastectomy rates were 37% and 34%, respectively. Five-year overall survival was 74% for AC and 82% for infusional ECisF (hazard ratio 0.76, 95% confidence interval 0.51-1.13; P = 0.18). Both treatments were well tolerated. Grade III/IV lethargy, vomiting, alopecia and plantar-palmar erythema were significantly greater for infusional ECisF; grade III/IV leucopenia was significantly greater for AC. CONCLUSIONS: Preoperative continuous infusional 5-FU-based chemotherapy is no more active than conventional AC for early breast cancer; with a median 5 year follow-up, the infusion-based schedule shows a non-significant trend towards improved survival.

Adult↗
PubMed2003

Is bicalutamide equivalent to goserelin for prostate volume reduction before radiation therapy? A prospective, observational study.

INTRODUCTION: We compare the cytoreductive efficacy of bicalutamide or goserelin with no hormonal manipulation in prostate cancer before brachytherapy. MATERIALS AND METHODS: Transrectal ultrasound volume estimations were performed in clinic and during the brachytherapy-planning scan. Between volume estimations, patients received no hormonal treatment, bicalutamide 150 mg once daily or goserelin 3.6 mg every 28 days. RESULTS: Patients receiving no hormonal manipulation had a volume increase of 8% compared with an 8% volume reduction in the bicalutamide group and a 26% reduction in the goserelin group. As initial prostate volume was not equivalent in the three groups, a subgroup analysis was performed on patients who received active treatment for more than 3 months who had initial prostate volume less than 55 cm3. In this subgroup, a mean fall in prostate volume of 7%, occurred in the bicalutamide group compared with 21% in the goserelin group. In both the original and subgroup analysis, the cytoreductive efficacy of goserelin was significantly greater than bicalutamide (P < 0.0001). CONCLUSION: In the absence of data from randomised trials, comparing the efficacy of these agents, luteinising hormone-releasing hormone (LHRH) analogues remain the gold standard for cytoreduction before prostate brachytherapy. If the neoadjuvant efficacy of hormonal manipulation in external beam radiotherapy is dependent on prostate volume reduction, then LHRH analogues may also prove more effective in this neoadjuvant role.

Analysis of Variance↗
PubMed2002

(125)Iodine prostate brachytherapy: outcome from the first 100 consecutive patients and selection strategies incorporating urodynamics.

OBJECTIVE: To report the results from the first 100 consecutive patients treated with 125I transperineal interstitial prostate brachytherapy between March 1999 and June 2001, and to determine if the International Prostate Symptom Score (IPSS), prostate volume or urodynamic variables correlate with acute morbidity. PATIENTS AND METHODS: Patients were assessed prospectively by uroflowmetry, the IPSS, a physical examination and transrectal ultrasonography. Of the 100 patients, 57 had a full urodynamic assessment, 61 presented with lower urinary tract symptoms (LUTS), 25 were screen-detected and 14 presented with other problems. The IPSS was recorded at 1, 6 and 12 weeks, and then at 3-monthly intervals after treatment; significant events, e.g. acute urinary retention (AUR) and rectal symptoms, were recorded prospectively; the mean follow-up was 16 months. RESULTS: No patients were incontinent after treatment. There was a temporary deterioration in IPSS in 89% of patients. Peak symptoms occurred at 6 weeks and a statistically significant deterioration in IPSS persisted until 9 months, but continued to improve throughout the follow-up. AUR affected seven patients, with a further 20 using clean intermittent self-catheterization (CISC) for symptoms. In most patients the symptoms resolved spontaneously to the levels before treatment, with only two patients requiring surgery for bladder outlet obstruction. The IPSS before treatment did not predict urodynamic obstruction. Urodynamically unobstructed patients did not require catheterization. By 2 years after implantation the mean IPSS was better than before treatment. Five patients had mild, transient proctitis. CONCLUSION: Selecting patients with a low prostate volume and IPSS is likely to optimize the outcome of brachytherapy. Urodynamic studies may be helpful in predicting the risk of AUR and symptoms requiring CISC. Despite many patients presenting with LUTS, acute morbidity was no worse than that reported in large American series of predominantly screening-detected cancers. Prostate brachytherapy is well tolerated and may be safely delivered to patients with prostate cancer in the UK.

Aged↗
PubMed2000

An audit of indications and techniques for supraclavicular fossa irradiation in early breast cancer in the United Kingdom.

This article describes an audit of the indications and techniques used by clinical oncologists in the United Kingdom (UK) in the delivery of adjuvant radiotherapy to the supraclavicular fossa (SCF) in patients with early breast cancer. A postal questionnaire was sent to one consultant clinical oncologist in each UK radiotherapy centre in November 1999. These were the same individuals listed in the Maher Committee Report as providing breast cancer services. Forty-one out of 51 completed forms were returned. The results show significant variation in the indications for SCF irradiation and for the definition of the radiotherapy target volume. We discuss the possible basis for the variations found in the audit. There was broad agreement on technique, in particular on the need for matching the tangential and SCF fields and maintaining patient position between fields, factors that are likely to minimize serious morbidity, including brachial plexus injury.

Breast Neoplasms↗
PubMed1997

Hypofractionated stereotactic radiotherapy in the management of recurrent glioma.

PURPOSE: This study aimed to assess the efficacy and toxicity of hypofractionated stereotactic radiotherapy (SRT) in the management of patients with recurrent glioma. METHODS AND MATERIALS: From January 1989 to July 1994, 36 patients with glioma were treated at the time of recurrence. Twenty-nine had recurrent high-grade astrocytoma, 3 high-grade oligodendroglioma, 1 high-grade ependymoma, and 3 pilocytic astrocytoma. Hypofractionated stereotactic radiotherapy was given using either three noncoplanar arcs or four to six noncoplanar fixed beams at 5 Gy/fraction, to doses ranging from 20 to 50 Gy initially on a dose escalation program. Two patients received 20 Gy, 8 received 30 Gy, 10 received 35 Gy, 10 received 40 Gy, 5 received 45 Gy, and 1 received 50 Gy, treating 5 days/week. RESULTS: The median survival of 29 patients with recurrent high-grade astrocytoma was 11 months from the time of SRT. This compared to a median survival of 7 months for a cohort matched for age, performance status, and initial histologic grade who received nitrosourea-based chemotherapy at recurrence (p < 0.05). Initial low-grade astrocytoma histology was the only favorable prognostic factor for survival on univariate analysis. Three patients with recurrent oligodendroglioma remain alive 11, 23, and 34 months after SRT. Three children treated for recurrent pilocytic astrocytoma remain alive 14, 41, and 55 months following SRT. Presumed radiation damage, defined as reversible steroid-dependent toxicity, was observed in 13 patients (36%) and required reoperation in 2 (6%). A total dose of >40 Gy was a major predictor of radiation damage (p < 0.005). CONCLUSION: Hypofractionated SRT is a noninvasive, well-tolerated, outpatient-based method of delivering palliative, high-dose, focal irradiation.

Adult↗
PubMed1994

Quality assurance in fractionated stereotactic radiotherapy.

The recent development of fractionated stereotactic radiotherapy (SRT), which utilises the relocatable Gill-Thomas-Cosman frame (GTC 'repeat localiser'), requires comprehensive quality assurance (QA). This paper focuses on those QA procedures particularly relevant to fractionated SRT treatments, and which have been derived from the technique used at the Royal Marsden Hospital. They primarily relate to the following: (i) GTC frame fitting, initially in the mould room, and then at each imaging session and treatment fraction; (ii) checking of the linear accelerator beam geometry and alignment lasers; and (iii) setting up of the patient for each fraction of treatment. The precision of the fractionated technique therefore depends on monitoring the GTC frame relocation at each fitting, checking the accuracy of the radiation isocentre of the treatment unit, its coincidence with the patient alignment lasers and the adjustments required to set the patient up accurately. The results of our quality control checks show that setting up to a mean radiation isocentre using precisely set-up alignment lasers can be achievable to within 1 mm accuracy. When this is combined with a mean GTC frame relocatability of 1 mm on the patient, a 2-mm allowance between the prescribed isodose surface and the defined target volume is a realistic safety margin for this technique.

Brain Neoplasms↗
PubMed1994

The significance of MALT histology in thyroid lymphoma: a review of patients from the BNLI and Royal Marsden Hospital.

Data from a series of 45 patients with Stage I and II non-Hodgkin's lymphoma (NHL) of the thyroid gland were analysed retrospectively to determine the incidence and prognostic significance of histopathological features of tumour origin from mucosa associated lymphoid tissue (MALT). The overall 5- and 10-year cause specific survival from NHL for the series was 79%. Evidence of tumour origin from MALT was the only significant prognostic factor for overall survival identified by multivariate analysis of the series (P < 0.01). A total of 31 (69%) tumours showed such evidence, the cause specific patient survival from NHL at 5 and 10 years being 90% compared with only 55% at 5 years for the 14 patients without such evidence. For patients given initial treatment with radiotherapy alone, those with evidence of tumour origin from MALT had a relatively low relapse rate and a relatively high success rate from salvage therapy, compared with a relatively high relapse rate and negligible success from salvage therapy in those without evidence of such tumour origin.

Adolescent↗
PubMed1994

Nodular basement membrane deposits in breast carcinoma and atypical ductal hyperplasia: mimics of collagenous spherulosis.

Collagenous spherulosis is characterised histologically by the accumulation of hyaline globules containing basement membrane components. Originally described in the breast, it has also been found in skin and salivary gland neoplasms. In the breast it has hitherto always been associated with benign disease and reports have asserted that this is invariably the case, cautioning against the diagnosis of malignancy when the condition is seen. We present here five cases with similar appearances to collagenous spherulosis in routine histology and immunohistochemistry, and ultrastructural studies in one of them, in which the condition was not associated with simple benign breast disease. Two of the cases were associated with invasive carcinomas of unusual histological types, one with intracystic papillary carcinoma, one with comedo ductal carcinoma-in-situ and one with atypical ductal hyperplasia. We suggest that appearances similar to collagenous spherulosis can be associated, either through being formed by a lesion or by collision, with malignancy and warn that on encountering the lesions the pathologist must not assume, as suggested in previous accounts, that it denotes a benign process. This is an important observation since collagenous spherulosis is likely to be encountered more frequently in the range of lesions biopsied in national breast screening programs.

Aged↗
PubMed1993

Efficacy and toxicity of fractionated stereotactic radiotherapy in the treatment of recurrent gliomas (phase I/II study).

Twenty-two patients with recurrent glioma have been treated on a dose escalation protocol with fractionated stereotactic external beam radiotherapy (SRT). All had previously received radical radiotherapy (median dose 55 Gy) as part of the initial treatment. The dose of SRT was increased from 30 Gy in six fractions to 50 Gy in ten fractions. Median survival from the date of SRT was 9.8 months. There was no significant acute morbidity but five patients who received > or = 40 Gy developed steroid responsive neurological deterioration assumed to represent late radiation damage. The survival and toxicity in patients with recurrent glioma are comparable with interstitial therapy. Fractionated SRT is a noninvasive form of localised radiation which may be a suitable alternative to interstitial therapy in this group of patients.

Adolescent↗