Report on the early efficacy and tolerability of I(125) permanent prostate brachytherapy from a UK multi-institutional database.

AIMS: To report the results of I(125) prostate brachytherapy from a central, prospectively collected database of three UK institutions. MATERIALS AND METHODS: All patients treated with I(125) permanent prostate brachytherapy at the Christie Hospital, Manchester (CHM), Cookridge Hospital, Leeds (CKL) and Mount Vernon Hospital, Northwood, London (MVL) since 2003 have been prospectively registered on a detailed central database. Patient, tumour, pre- and post-implant dosimetry data have been recorded. Urinary toxicity as assessed by the International Prostate Symptom Score, catheterisation and urinary stricture rates after implant have been documented and biochemical failure determined, using both the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and the Phoenix (nadir + 2 ng/ml) definition. RESULTS: In total, 1535 patients were registered on the database between January 2003 and October 2006, including 432 from CHM, 926 from CKL and 177 from MVL, with a median follow-up of 21 months (range 1-56). Patient and tumour characteristics were similar at all centres. Pre-implant dose indices were comparable between centres, except for the V150, with median values of 51.9, 64.3 and 69.8% at CHM, CKL and MVL, respectively. Median post-implant dose parameters were lower than pre-planned constraints by up to 33.0% at each centre for all values, except at CKL where the V200 was 23.9% higher. The International Prostate Symptom Score increased from a median of 5 at baseline to 18, 6 weeks after implant, but was not significantly different to baseline values by 12 months. Nine per cent of men required catheterisation after implant for a median duration of 53 days, but urinary stricture rates remained low at 1%. Neoadjuvant hormonal manipulation was used in 228 men (15%) for downsizing and 159 (10%) for intermediate/high-risk disease. Collated biochemical failure rates were low at this point of follow-up, with actuarial 2-year ASTRO and Phoenix biochemical failure-free survival rates of 94.4 and 94.5%, respectively, consistent with other large single centre reports. When post-implant dosimetric factors were assessed for a relationship to biochemical failure, no indices consistently predicted for improved ASTRO and Phoenix biochemical failure-free survival rates. CONCLUSIONS: This ongoing collaboration shows that with limited infrastructure (a single industry-sponsored data manager), a large multi-institutional database estimated to represent one-third of implants carried out in the UK during this time can be developed. Patient selection was similar across all centres and adhered to published guidelines. Early biochemical and toxicity outcomes confirm the efficacy and tolerability of I(125) prostate brachytherapy in a large cohort of patients. A further analysis is planned.

When should the seminal vesicles be included in the target volume in prostate radiotherapy?

External beam radiotherapy to the prostate and seminal vesicles as a radical treatment for prostate cancer can result in a significant dose being delivered to the rectum. This can be reduced if the target volume includes the prostate only. Using a Medline search, published studies are reviewed to show that the risk of seminal vesicle involvement can be accurately predicted using readily available pre-treatment parameters. We recommend when to exclude the seminal vesicles from a target volume, and the proportion of seminal vesicles that should be included in a target volume in higher risk patients.

Fibromatosis: benign by name but not necessarily by nature.

Aggressive fibromatoses, also known as desmoid tumours, are rare fibrous tissue proliferations with a tendency for slow, local infiltrative growth. There is an association with Gardner's syndrome and familial adenomatous polyposis. Histologically they are fairly bland with no abnormal mitoses or necrosis. They do not metastasize, but can cause significant morbidity through their locally destructive effects. Magnetic resonance imaging is the method of choice for diagnosis, pre-treatment planning and post-treatment follow-up. Surgical excision with a wide margin is the treatment of choice. However, there is a tendency for local recurrence and repeated excision may result in a poor functional or cosmetic outcome. Radiotherapy is used to reduce local recurrence rates after excision and is also used to treat inoperable tumours. Long-lasting remissions can be obtained. Treatment is now planned using modern three-dimensional conformal techniques, similar to those used in soft tissue sarcoma management. There is no definite dose-response relationship, but doses of 50-60 Gy in 1.8-2 Gy fractions are recommended. Systemic therapy has been used for lesions not controlled by surgery or radiotherapy, or less commonly, as a primary treatment. Tamoxifen and non-steroidal anti-inflammatory agents are used most often as they are relatively non-toxic, but there is limited experience with cytotoxic chemotherapy and biological agents. There are no randomised trials to help guide the management of this locally aggressive 'benign' tumour and treatment decisions are best made by the local soft tissue sarcoma multidisciplinary team.

A national survey of current practices of preparation and management of radical prostate radiotherapy patients during treatment.

AIMS: Radiotherapy is an important radical treatment for prostate cancer patients with services continually evolving. This survey aims to gain an insight in to the variation of radiotherapy practices in the UK, focussing on pre-treatment preparations, on-treatment review and management of radical prostate cancer patients undergoing radiotherapy. To our knowledge this is the first survey reported focussing on prostate radiotherapy practices with responses from a mix of health professionals. MATERIALS AND METHODS: A national survey was designed based on current known practices in supportive care and management of prostate cancer patients. The survey was distributed to lead radiotherapy personnel in radiotherapy services across the UK with a 77% response rate (n = 54). RESULTS: Pre-treatment protocols were mandated in the majority of departments. Use of bladder filling (98%) and bowel emptying (66%) were frequently deployed. Bowel preparation varied between use of laxatives (13%) or enemas (41%) to achieve consistency. On-treatment reviews were carried out by a mix of health professionals; most commonly shared between oncologists and radiographers (20%). Radiographers reviewing patients were independent prescribers in 22% of departments. Toxicity grading tools were not used by almost half of departments (47%) either at baseline and/or on-treatment reviews. Written information about follow-up was given to patients towards the end of their radiotherapy; however, fewer departments included the length of hormone duration (13%). CONCLUSION: This survey has demonstrated variations in practice exist across the UK. These variations suggest that important questions about the best methods for treatment accuracy and patient management need to be established through further research.

External-beam radiotherapy in T1-2 N0 penile carcinoma.

AIMS: To review the outcome of 41 patients with invasive carcinoma of the penis treated with external-beam radiotherapy using a consistent technique and dose. MATERIALS AND METHODS: Forty-one patients with carcinoma of the penis treated at Christie Hospital, Manchester, UK, between 1995 and 2000 were reviewed retrospectively. Radiotherapy was delivered using 4 MV linear accelerators with a dose of 50 Gy or 52.5 Gy in 16 fractions over 22 days. RESULTS: The distribution of patients according to stage was T1=37, T2=4, N0=40, N3=1. Median follow-up was 4.5 years. The local control rate was 62%, nodal relapse-free rate of 88%, relapse-free rate of 51% and overall survival of 88% at 5 years. All recurrences were salvaged by surgery. Penile ulceration occurred in 8% and urethral stenosis requiring dilatation in 29%. There were no penectomies for penile necrosis. CONCLUSION: EBXRT may be offered for T1-2 cancer of the penis with close surveillance to detect local recurrences early for salvage surgery without jeopardising overall survival. It remains an alternative option to penis-preserving surgery and should be discussed in a multidisciplinary setting and with the patient.

Prediction of urinary symptoms after 125iodine prostate brachytherapy.

AIMS: To evaluate the post-treatment urinary morbidity experienced by a cohort of men undergoing ultrasound-based transperineal prostate brachytherapy, as monotherapy for early stage carcinoma of the prostate. MATERIALS AND METHODS: One hundred and thirty-four consecutive patients received prostate brachytherapy between March 2000 and July 2002, and were asked to complete the International Prostate Symptom Score (IPSS) and Hospital Anxiety and Depression (HAD) questionnaires before treatment and at 1, 3, 6, 9, 12 and 18 months after implant. Data on catheterisation and surgical interventions were also recorded. Pre-treatment IPSS, dosimetry and other variables were analysed in relation to catheterisation rates and post-treatment IPSS scores at each time window. RESULTS: One hundred and eleven patients returned sufficient data for meaningful analysis. Of the patients who completed IPSS at 1 month, 85 (97%) reported deterioration in IPSS scores. This peak of symptoms, identified by a rise in median IPSS, started to improve by 3 months, and was approaching baseline by 18 months. The only significant determinants of early urinary toxicity were pre-treatment IPSS, pre-treatment prostate volume and the difficulty of implant. However, prostate volume was not significant beyond 1 month. Twenty-six patients required catheterisation at a median of 10 days after implant. Significant predictors of urinary retention were pre-treatment prostate volume and pre-treatment IPSS. Patients requiring catheterisation continued to have significantly higher IPSS at 18 months than patients who had never required a catheter. CONCLUSION: Brachytherapy was generally well tolerated, with urinary toxicity in most patients persisting for at least 3-6 months after prostate brachytherapy. Those whose pre-treatment prostate volume and IPSS were high experienced more severe urinary symptoms in the first few months.

Adjuvant and salvage treatment after radical prostatectomy: current practice in the UK.

OBJECTIVE: To survey UK urologists and radiation oncologists in the evaluation and treatment of localised prostate cancer in the adjuvant and salvage setting. METHODS: Postal questionnaires were mailed to 292 urologists and 98 radiation oncologists in the UK. RESULTS: In all, 188 (48%) questionnaires were returned. In total, 72/128 (56%) of the urologist respondents and 58/60 (97%) of the oncologist respondents perform routine radical prostate treatment. Among 43 (60%) of the urologist, 40 (69%) recommended adjuvant treatment, which could be radiotherapy, hormonal treatment or combined hormonal and radiation treatment. There is no significant difference between the modality of treatment recommended. The poor prognostic factors that would influence the decision to offer adjuvant treatment include a detectable postoperative PSA, seminal vesicle involvement, positive margins, Gleason score>8 and pathological T3. With regard to the choice of hormonal treatment, most urologists preferred antiandrogens, whereas most oncologists prefer lutienising hormone releasing hormone (LHRH) analogue (P=0.03). Regarding salvage treatment, there is a wide variation in the PSA threshold and number of PSA rises before initiation of investigations and treatment. Significantly more urologists recommended salvage radiotherapy (P=0.02), whereas oncologists recommended combined hormonal radiation therapy (P=0.03). There is a wide variation of practice regarding the duration of hormonal treatment, the type of investigations initiated, range of radiotherapy doses and treatment volumes. CONCLUSION: There is a wide variation in practice among UK clinicians.

The role of radiotherapy in the treatment of localised intermediate and high grade non-Hodgkin's lymphoma in elderly patients.

BACKGROUND AND PURPOSE: The treatment of elderly patients with high or intermediate grade non-Hodgkin's lymphoma (NHL) remains difficult and controversial. In order to audit our own practice, 270 elderly patients treated between 1988 and 1993 with this diagnosis were retrospectively reviewed. MATERIAL AND METHODS: 81 patients unfit for chemotherapy received fractionated radiotherapy for apparently localised stage I or II disease. The median age of the patients was 78 years (range 70-87 years). Forty stage I and 17 stage II patients had extra-nodal sites of disease. The radiation field included the primary site plus immediate adjacent nodes. RESULTS: After a median follow-up of 3.9 years the 5-year overall and disease-free survival rates were 33% and 31%, respectively. Age (hazard ratio (HR) 1.22, P = 0.03), stage (HR 5.50, P = 0.02) and lactate dehydrogenase level (HR 1.003, P = 0.004) were identified as independent risk factors for relapse. CONCLUSION: These factors can define a group in which radiotherapy can produce acceptable survival rates (age < or = 80 years, stage I and lactate dehydrogenase < or = 500). This group represented 34% of those patients where all these variables were recorded and had 5-year disease-free and overall survival rates of 56% and 62%, respectively.

Definitive radiotherapy for 114 cases of T3N0 glottic carcinoma: influence of dose-volume parameters on outcome.

BACKGROUND AND PURPOSE: Assuming that the dose-response curve for T3N0M0 glottic carcinoma is steep and that the rate of occult lymph node metastases is low, it should be possible to employ high biological tumour doses to modest target volumes and thereby maximise laryngeal control without compromising final neck control. Within the constraints of a retrospective study we aim to examine this policy with respect to local control, incidence of nodal relapse and late complications. MATERIALS AND METHODS: One hundred and fourteen patients with T3N0M0 glottic carcinoma who received a 3-week schedule of radical radiotherapy between 1986 and 1994 were analysed. The median age was 67 years (range, 34-85 years) and the median follow-up for living patients was 4.8 years (1.9-8.9 years). There were no strict selection criteria for those patients treated with radiotherapy. RESULTS: The 5-year overall survival was 54%. The 5-year local control with radiotherapy and the ultimate loco-regional control following salvage laryngectomy were 68 and 80%, respectively. Nine patients (8%) suffered a regional nodal relapse but only three of these (3% overall) occurred in the absence of local failure. Four patients (3.5%) developed serious late complications requiring surgical intervention (three received 55 Gy and one 52.5 Gy). CONCLUSIONS: It is possible to employ maximum tolerable doses to specific target volumes and thereby exploit the dose response demonstrated and minimise major late effects. The use of modest target volumes resulted in only 3% of patients requiring surgery that might have been avoided had prophylactic neck irradiation been employed.

Pitfalls of hCG monitoring in stage I seminoma.

We detail the case history of a patient with Stage I seminoma, who developed an elevated level of human chorionic gonadotrophin (hCG) while on follow-up. It transpired that the patient had injected himself with hCG several days before. This type of abuse has been documented, but this is the first reported case of it interfering with the follow-up of a patient with a germ cell tumour.

Intracranial juvenile nasopharyngeal angiofibroma.

We report the case history of a 26-year-old man who was diagnosed with advanced juvenile nasopharyngeal angiofibroma with intracranial extension. The lesion was considered to be inoperable and the patient was treated with radical radiotherapy. Serial magnetic resonance imaging has shown continued tumour regression and he remains well after 3 years. The literature is reviewed and radiotherapy recommended as the modality of choice for these patients.

Hypofractionated radiotherapy as salvage for rising prostate-specific antigen after radical prostatectomy.

AIMS: To review the outcome of men receiving hypofractionated salvage radiotherapy for rising prostate-specific antigen (PSA) after radical prostatectomy. MATERIALS AND METHODS: A retrospective analysis of 61 men referred for salvage radiotherapy for biochemical relapse after radical prostatectomy was conducted. Twenty-four men receiving hormonal therapy or with follow-up of less than 12 months were excluded. Thirty-seven men were identified, median age 64 years, median preoperative PSA 11 ng/ml (5.6-60 ng/ml), Gleason scores <7: 70%, Gleason scores > or = 7: 30%. Twenty-seven men had positive surgical resection margins, eight had seminal-vesicle involvement and one had lymph-node involvement. Diagnosis of failure after radical prostatectomy was made on rising PSA in all cases; 19 men also had positive magnetic resonance imaging, 11 abnormal digital rectal examination and nine positive biopsy. Radiotherapy was delivered conformally to the prostatic fossa, 50-52.5 Gy in 20 fractions over 4 weeks. Date of failure after radiotherapy was defined by the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria or as date of commencement of hormonal therapy for rising PSA. RESULTS: Median time from radical prostatectomy to radiotherapy was 30.6 months (8-68 months); median pre-radiotherapy PSA was 2.9 ng/ml (0.5-11.4 ng/ml). PSA response after radiotherapy was seen in 33 out of 37 (89%) patients. At median follow-up of 36 months (20-85 months), 28 out of 37 remained disease-free. Thirteen more patients have had two consecutive PSA rises. Actuarial 3-year disease-free survival is 74%. No patient has developed metastases or died of prostate cancer. Pre-radiotherapy PSA less than 2 ng/ml predicted disease-free survival (P = 0.027). No acute toxicity greater than Radiation Therapy Oncology Group (RTOG) G2 was observed. CONCLUSIONS: Salvage radiotherapy after radical prostatectomy achieved durable biochemical control in most patients. Outcome is improved if radiotherapy is delivered when PSA is less than 2 ng/ml. A policy of close monitoring after radical prostatectomy with early referral for salvage radiotherapy is advocated.

Small-cell carcinoma of the urinary bladder: 10-year experience.

AIMS: Small-cell carcinoma of the urinary bladder is rarely encountered in clinical practice. We report on our clinical experience with affected patients presenting to our institution from 1986 to 1996. MATERIALS AND METHODS: We retrospectively analysed 14 pathologically confirmed cases, specifically looking at stage, presenting features, treatment and overall survival. The median age at presentation was 74 years (range 54-91 years). RESULTS: Ten patients presented with stage III disease, and four patients with stage IV disease (1 = nodal, 3 = distant metastases). Four patients were treated with radical radiotherapy (one patient receiving neoadjuvant chemotherapy) and two underwent a radical cystoprostatectomy. Five patients received palliative bladder radiotherapy and three were too frail for treatment at presentation. The overall median survival was 5 months. Patients receiving radical treatment had a median overall survival of 21 months, with only one long-term survivor. CONCLUSION: This highly aggressive tumour tends to affect an elderly population who are generally frail and have significant comorbidity. Many are unfit for radical treatment. In patients with disease confined to the pelvis who are able to tolerate radical intervention, the results of local therapy alone are poor. It therefore remains incumbent on treating clinicians to explore means of improving these results. Initial chemotherapy analogous to small-cell lung cancer may offer a durable response with a better chance for long-term survival.

A doxorubicin-based regimen used in the treatment of elderly patients with high-grade non-Hodgkin's lymphoma.

A retrospective analysis was performed on 66 patients, aged 70 years or older, who received treatment with a weekly doxorubicin-containing regimen (VAPEC-B) for high grade non-Hodgkin's lymphoma (NHL). Two dosing schedules were employed. The choice of regimen was at the discretion of the treating clinician and reflected the performance status of the patient and the predicted tolerance to chemotherapy. Forty-nine patients received a half-dose schedule and 17 the full-dose schedule. Those receiving the half-dose regimen had a lower median performance status and received a lower dose intensity of chemotherapy (45% versus 83%). However, the outcomes of the two groups were similar: complete remission rate 41% versus 47%, and 5-year overall survival 36% versus 23%, for the half- and full-dose groups, respectively. A similar proportion of patients (51% versus 59%) completed each regimen, although there were more delays in treatment delivery experienced in those receiving the full dose. Half-dose VAPEC-B is an effective treatment option for elderly patients with high-grade NHL and has comparable efficacy with other published regimens. The use of such low-dose doxorubicin-containing regimens in elderly patients with high-grade NHL requires further investigation.

Contemporary radiotherapy for soft tissue sarcoma.

This review will detail the role of radiotherapy in the management of soft tissue sarcoma. Particular emphasis will be given to its role as an adjuvant to surgical excision for local curative management. The addition of radiotherapy permits a tissue-conserving operation to be performed, which has functional and cosmetic advantages yet produces local control equivalent to more radical surgery alone. The review will consider the historical evolution of treatment up through recent and contemporary practice. The principles of use will be outlined using available evidence and, where this is lacking, it will be acknowledged with suggestions for improvement. Finally, a brief overview of some technical issues about radiotherapy will be provided.