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Biomedical subjects

J P Logue

Publications and source records attributed to J P Logue.

At least 19 recordsLinked to original sources

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.

Carcinoma, Squamous Cell↗

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.

Aged↗

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.

Chemotherapy, Adjuvant↗

Controversies in the radiotherapeutic management of poor prognosis locally advanced prostate cancer.

The Grand Round was held at the Christie Hospital, Manchester, U.K., on 30 November 2002. It followed a presentation by Dr David Dearnaley from the Royal Marsden Hospital in Sutton on 'Novel approaches and trials in prostate cancer'. Controversies in the management of locally advanced prostate cancer were illustrated by a case presentation and followed by a discussion on the evaluation of disease extent, and the roles of radiotherapy and hormone ablation.

Androgen Antagonists↗

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.

Aged↗

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.

Aged↗

Live birth with sperm cryopreserved for 21 years prior to cancer treatment: case report.

Advances in cancer treatment have led to significant improvements in the likelihood of reaching remission and long-term survival for men. Chemo- and radiotherapy-induced infertility are significant treatment side effects. Cryopreservation before the start of treatment enables sperm to be stored, thereby preserving the man's potential fertility. Here, we describe the successful use (with ICSI) of sperm cryopreserved prior to cancer treatment, for a total of 21 years. We believe this to be the longest period of sperm cryopreservation, resulting in a live birth, so far reported in the literature.

Adolescent↗

Development of a simultaneous boost IMRT class solution for a hypofractionated prostate cancer protocol.

The purpose of this work was to develop a robust technique for planning intensity-modulated radiation therapy (IMRT) for prostate cancer patients who are to be entered into a proposed hypofractionated dose escalation study. In this study the dose escalation will be restricted to the prostate alone, which may be regarded as a concurrent boost volume within the overall planning target volume (PTV). The dose to the prostate itself is to be delivered in 3 Gy fractions, and for this phase of the study the total prostate dose will be 57 Gy in 19 fractions, with 50 Gy prescribed to the rest of the PTV. If acute toxicity results are acceptable, the next phase will escalate doses to 60 Gy in 20 x 3 Gy fractions. There will be 30 patients in each arm. This work describes the class solution which was developed to create IMRT plans for this study, and which enabled the same set of inverse planning parameters to be used during optimization for every patient with minimal planner intervention. The resulting dose distributions were compared with those that would be achieved from a 3D conformal radiotherapy (3DCRT) technique that used a multileaf collimator (MLC) but no intensity modulation to treat the PTV, followed by a sequential boost to raise the prostate to 57 Gy. The two methods were tested on anatomical data sets for a series of 10 patients who would have been eligible for this study, and the techniques were compared in terms of doses to the target volumes and the organs at risk. The IMRT method resulted in much greater sparing of the rectum and bladder than the 3DCRT technique, whilst still delivering acceptable doses to the target volumes. In particular, the volume of rectum receiving the minimum PTV dose of 47.5 Gy was reduced from a mean value of 36.9% (range 23.4% to 61.0%) to 18.6% (10.3% to 29.0%). In conclusion, it was found possible to use a class solution approach to produce IMRT dose escalated plans. This IMRT technique has since been implemented clinically for patients enrolled in the hypofractionated dose escalation study.

Clinical Protocols↗

Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix.

There is increasing evidence that hypoxia-regulated gene expression influences tumor aggressiveness, contributing to the poorer outcome of patients with hypoxic tumors. The role of the transcriptional complex hypoxia-inducible factor-1 as an important mediator of hypoxia-regulated gene expression is one of the best documented pathways. Recently, it has emerged that certain tumor-associated carbonic anhydrases (CAs) can be added to the list of known hypoxia-inducible factor-responsive genes. Here we show that the immunohistochemical expression of the tumor-associated CA IX is correlated with the level of hypoxia in human cervical tumors. We performed a prospective study in 68 patients where needle electrodes were used to make direct measurements of tumor oxygenation levels. CA IX expression was evaluated immunohistochemically in pretreatment tumor biopsies. There was a significant positive correlation between the level of tumor hypoxia (HP5) and the extent of CA IX expression. A retrospective study of 130 squamous cell cervical carcinomas demonstrated that a semiquantitative immunohistochemical analysis of CA IX expression in tumor biopsies is a significant and independent prognostic indicator of overall survival and metastasis-free survival after radiation therapy. These studies provide clinical evidence that CA IX expression is up-regulated in hypoxic human cervical tumors and is associated with a poor prognosis. CA IX may act as an intrinsic marker of tumor hypoxia and poor outcome after radiation therapy. The level of CA IX expression may be used to aid in the selection of patients who would benefit most from hypoxia-modification therapies or bio-reductive drugs.

Antigens, Neoplasm↗

Patient positioning using detailed three-dimensional surface data for patients undergoing conformal radiation therapy for carcinoma of the prostate: a feasibility study.

PURPOSE: The increasing complexity of radiotherapy highlights the need for accurate setup. This paper assesses the potential of position corrections, derived from the three-dimensional (3D) surface of the patient, in reducing positioning errors in patients undergoing conformal radiation therapy of the prostate. METHODS AND MATERIALS: Twenty patients undergoing conformal radiation therapy for prostate cancer had planning computed tomography (CT) scans and then weekly treatment CT scans over the course of their treatment. Patients were positioned on the CT table using three coplanar tattoo marks used for patient setup on the accelerator. Surfaces were computed from the planning CT (planning surface), and the treatment CT (treatment surfaces). Using a surface matching utility, the planning and treatment 3D surfaces were compared. The prostate was implicitly localized based on surface matching of the external contour and by matching the bony anatomy. The resultant prostate displacement after correction was assessed for the two localization methods. RESULTS: Correcting patient position via the surface comparisons reduced the standard deviation of prostate displacement with respect to the patient isocenter in the lateral and anterior/posterior directions. In the lateral direction, prostate and surface motion was highly correlated (r = 0.96). In the anterior/posterior direction the corrections from the surface data were as effective as those derived from the bony anatomy. CONCLUSION: Detailed surface data can aid the positioning of patients receiving conformal radiation therapy to the prostate by reducing the displacement of the target from the intended treatment position. This study shows that surface corrections can be as effective as those derived from bony anatomy, and may be exploited where definition of bony anatomy is difficult.

Feasibility Studies↗

Clinical implementation of dynamic multileaf collimation for compensated bladder treatments.

BACKGROUND AND PURPOSE: To describe the clinical implementation of dynamic multileaf collimation (DMLC). Custom compensated four-field treatments of carcinoma of the bladder have been used as a simple test site for the introduction of intensity modulated radiotherapy. MATERIALS AND METHODS: Compensating intensity modulations are calculated from computed tomography (CT) data, accounting for scattered, as well as primary radiation. Modulations are converted to multileaf collimator (MLC) leaf and jaw settings for dynamic delivery on a linear accelerator. A full dose calculation is carried out, accounting for dynamic leaf and jaw motion and transmission through these components. Before treatment, a test run of the delivery is performed and an absolute dose measurement made in a water or solid water phantom. Treatments are verified by in vivo diode measurements and real-time electronic portal imaging. RESULTS: Seven patients have been treated using DMLC. The technique improves dose homogeneity within the target volume, reducing high dose areas and compensating for loss of scatter at the beam edge. A typical total treatment time is 20 min. CONCLUSIONS: Compensated bladder treatments have proven an effective test site for DMLC in an extremely busy clinic.

Carcinoma↗

Patterns of relapse following radiotherapy for stage I seminoma of the testis: implications for follow-up.

A retrospective review was undertaken of 409 consecutive patients treated with adjuvant radiotherapy for Stage I seminoma between 1988 and 1997. A total of 339 men were treated to a volume encompassing the para-aortic nodes and 70 were treated with extended field radiotherapy. The patients were followed up within oncology clinics adhering to a standard protocol of clinical examination, chest radiography and measurement of serum marker levels. No routine computed tomographic (CT) scans were carried out. At a median follow-up of 57 months, 13 patients have relapsed, giving a recurrence-free rate of 97.2% at 3 years and 96.8% at 5 years. Of these, eight (62%) were detected at routine appointments and five (38%) requested early appointments. Chest radiography (2/5) and serum marker levels (3/5) identified disease in asymptomatic patients. Eight patients (62%) had raised markers at relapse, including two with normal serum markers at original presentation. The median size of pelvic node recurrences in the para-aortic-treated group was 7.3 cm (2.8-13 cm). Four patients have developed second testicular primaries: three were detected at routine appointments and one patient had requested an early appointment. We conclude that regular follow-up with serum marker estimations and chest radiography is sufficient to detect recurrence at an early stage and that our policy of no routine CT scanning has been shown to give acceptable results.

Biomarkers, Tumor↗

The effect of radiotherapy treatment changes on sites of relapse in stage I testicular seminoma.

AIM: To evaluate relapse patterns in stage I testicular seminoma related to changes in radiotherapy practice. METHOD: Four hundred and six patients with stage I testicular seminoma were treated with adjuvant radiotherapy following orchidectomy: 338 patients received para-aortic radiotherapy only and 68 patients with added risk factors had radiotherapy extended to include the pelvis. Computed tomograms of relapsed patients were reviewed and sites of relapse were documented with correlation to the radiotherapy field. RESULTS: Thirteen relapses were identified; 10 occurring in the para-aortic radiotherapy group (3.0% relapse rate) and three in the extended radiotherapy field group (4.4% relapse rate). Sites of relapse were; five pelvis, three mediastinum, one lung, one scapula, one scrotum, while one patient had multiple relapse sites including the pelvis and one had a tumour marker relapse with no site identified. All the pelvic relapses occurred in the para-aortic radiotherapy group. CONCLUSION: Pelvic relapse only occurred when radiotherapy had been confined to the para-aortic region. Since para-aortic radiotherapy achieves equivalent outcome to wider field radiotherapy with reduced toxicity, it is likely to become standard practice in stage I seminoma and pelvic relapses will therefore increase in frequency. It is therefore important to include pelvic imaging when relapse is suspected.

Adult↗

Tumour oxygenation levels correlate with dynamic contrast-enhanced magnetic resonance imaging parameters in carcinoma of the cervix.

BACKGROUND AND PURPOSE: The Eppendorf pO(2) histograph is the 'gold standard' method for measuring tumour oxygenation. The method is not suitable for widespread application because its use is limited to accessible tumours. A non-invasive imaging technique would be an attractive alternative. Therefore, the relationships between tumour oxygenation and dynamic contrast-enhanced magnetic resonance imaging (MRI) parameters were investigated. MATERIALS AND METHODS: The study comprised 30 patients with carcinoma of the cervix. Tumour oxygenation was measured pre-treatment as median pO(2) and the proportion of values less than 5 mmHg (HP5) using a pO(2) histograph. Repeat measurements were obtained for nine patients following 40-45 Gy external beam radiotherapy giving a total of 39 measurements. Dynamic contrast-enhanced MRI using gadolinium was performed prior to obtaining the oxygenation data. Time/signal intensity curves were generated to obtain two standard parameters: maximum enhancement over baseline (SI-I) and the rate of enhancement (SI-I/s). RESULTS: Using the 39 measurements, there was a significant correlation between SI-I and both median pO(2) (r=0.59; P<0.001) and HP5 (r=-0. 49; P=0.002). There was a weak, borderline significant correlation between SI-I/s and both median pO(2) (r=0.29; P=0.071) and HP5 (r=-0. 34; P=0.037). There was a significant relationship between tumour size and SI-I (r=0.54; P<0.001), but not SI-I/s. In 29 tumours, where data were available, there was no relationship between histological assessment of tumour angiogenesis (intra-tumour microvessel density; IMD) and either MRI parameter. CONCLUSIONS: Tumour oxygenation levels measured using a pO(2) histograph correlate with dynamic contrast-enhanced MRI parameters. Therefore, non-invasive dynamic MRI may be a method for measuring hypoxia in human tumours.

Adult↗

Relationship of MRI and clinical staging to outcome in invasive bladder cancer treated by radiotherapy.

AIM: To compare MRI and clinical staging of invasive bladder cancer prospectively and identify additional prognostic features on MRI before radiotherapy. METHODS AND MATERIALS: 143 patients with a pathological diagnosis of transitional cell carcinoma underwent MRI (1.0 T) of the abdomen and pelvis before radical radiotherapy. Tumour size, site, degree of infiltration, presence of adenopathy and hydronephrosis were assessed and an appropriate radiological stage assigned. Following radiotherapy all patients received regular cystoscopic follow-up. Date of first relapse and date of death were recorded. RESULTS: The median follow-up was 2.8 years for survivors. Those patients upstaged from T2a clinically to T3b on MRI had a significantly worse outcome (P = 0.0078). In univariate analysis a number of MRI features were significantly associated with adverse outcome: tumour size, circumferential tumour extent, and presence of hydronephrosis (all P < 0.05). After adjustment for clinical T stage and histological grade, all these MRI features and the MRI T stage were found to confer additional prognostic information in predicting early disease relapse and death (P < 0.05). CONCLUSION: This study demonstrates that MRI before radiotherapy provides valuable additional prognostic information compared to clinical staging.

Aged↗