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Biomedical subjects

R P Symonds

Publications and source records attributed to R P Symonds.

At least 19 recordsLinked to original sources
PubMed2006

Chemotherapy for advanced, recurrent or metastatic endometrial cancer: a systematic review of Cochrane collaboration.

BACKGROUND: Cytotoxic chemotherapy has a limited place in the management of advanced or recurrent endometrial cancer. Commonly used agents include cisplatin and doxorubicin, but the side-effect profile may be unacceptable for many patients. The feasibility of administration of combination chemotherapy is limited in many patients on account of significant co-morbidity. While early-stage endometrial adenocarcinoma is a common gynaecological cancer with a favourable prognosis, advanced or recurrent disease presents a difficult management problem. The platinum and anthracycline compounds have been widely used for many years, but their impact on progression-free survival (PFS) and overall survival (OS) is not clear. This systematic review aimed to evaluate both the benefits and adverse effects of cytotoxic chemotherapy in these women. PATIENTS AND METHODS: We carried out systematic searches for randomised controlled trials (RCTs) comparing chemotherapy with another intervention. Data were extracted from trial reports or supplied by investigators. Where possible, hazard ratios (HRs) were calculated for OS and PFS and odds ratios (ORs) were calculated for acute toxicity. The impact of more versus less intensive chemotherapy on OS, PFS and acute toxicity was assessed in a meta-analysis. RESULTS: Eleven eligible RCTs were identified that recruited 2288 patients. A meta-analysis of six of these trials found that PFS [HR = 0.80, 95% confidence interval (CI) 0.71-0.90; P = 0.004], but not OS (HR = 0.90, 95% CI 0.80-1.03; P = 0.12), was significantly improved when more intensive chemotherapy was compared with less intensive chemotherapy. OS was improved when doxorubicin, cisplatin and other drugs were compared with doxorubicin and cisplatin. Toxicity was generally higher with more chemotherapy. There was insufficient evidence to assess the effect of chemotherapy on symptom control or quality of life (QoL). Platinums, anthracyclines and taxanes were the most studied in phase II trials and combinations gave the best responses, but patient selection and pre-treatment was very variable. CONCLUSIONS: More intense combination chemotherapy significantly improves the disease-free survival and the data indicate a modest improvement in OS. The addition of anthracyclines (e.g. doxorubicin) or the taxanes [e.g. paclitaxel (Taxol)] to cisplatin increases the response rate. More intensive regimens are associated with the gain in survival. However, grade 3 and 4 myelosuppression and gastrointestinal toxicity are also increased. Future developments are likely to exploit specific molecular characteristics of endometrial cancers, including their hormone dependence, growth factor target overexpression and PTEN loss. While no one drug or regimen offers a clear benefit for women with advanced endometrial cancer, platinum drugs, anthracyclines and paclitaxel seem the most promising agents. Future trials should address the impact of such agents on QoL and symptom control in addition to survival. Chemotherapy and endocrine therapy need to be compared directly in an RCT.

Antineoplastic Agents↗
PubMed2006

Dermatomyositis as a paraneoplastic syndrome in carcinosarcoma of uterine origin.

Paraneoplastic syndromes are a collection of disorders affecting an organ or tissue caused by cancer but occurring at a site distant from the primary or metastases. Dermatomyositis can occur in association with malignancy as a paraneoplastic phenomenon. We present a case of a patient presenting simultaneously with an advanced carcinosarcoma of the uterus and dermatomyositis. The diagnoses, pathophysiology and treatment of these two conditions are discussed and current published studies reviewed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Epidermal growth factor receptor status predicts local response to radical radiotherapy in muscle-invasive bladder cancer.

AIMS: Epidermal growth factor receptor (EGFR) is expressed by over 70% of muscle-invasive bladder tumours and is associated with diminished overall survival. In model tumour systems, ionising radiation has been shown to activate EGFR, leading to cellular proliferation and is therefore a possible mechanism of underlying radioresistance. We carried out an immunohistochemical study relating the clinical outcome of patients receiving radical radiotherapy for muscle-invasive bladder cancer to tumour EGFR status. MATERIALS AND METHODS: Archived paraffin-embedded tumours from 110 consecutive patients receiving radical radiotherapy for muscle-invasive bladder cancer between 1991 and 1997 were immunohistochemically stained for EGFR. Data were collected concerning the tumour stage and grade, the presence of ureteric obstruction, the response to radiotherapy at 3 months, local recurrence rates, metastatic spread and survival. Multivariate analysis of potential independent prognostic factors of impaired bladder cancer-specific survival was carried out using Cox's regression. RESULTS: Of 110 tumours, 79 (72%) stained positively for EGFR. Of 87 patients undergoing the 3-month check cystoscopy, 60 (69%) had a positive response to radiotherapy. A positive response to radiotherapy correlated significantly with a negative EGFR status (chi(2) test, P = 0.05). Kaplan-Meier survival analysis revealed a trend towards improved bladder cancer-specific survival in EGFR-negative patients (Log-rank, P = 0.10). A lack of response to radiotherapy at 3 months, local recurrence, metastatic spread and the presence of ureteric obstruction were all independent prognostic factors for diminished bladder cancer-specific survival (Cox's regression: P = 0.009, P = 0.001, P = 0.04 and P = 0.005, respectively). CONCLUSIONS: EGFR status predicts the local response to radiotherapy but does not provide prognostic utility in relation to overall or bladder cancer-specific survival. As EGFR status seems to be linked to the initial response to radiotherapy, its inhibition may be a means of enhancing the radio-responsiveness of these poor prognosis tumours. Colquhoun, A. J.

Aged↗
PubMed2005

Radiotherapy to patients with artificial cardiac pacemakers.

BACKGROUND: The in vitro studies show that the modern cardiac pacemakers utilising the complementary metal-oxide semi-conductor (CMOS) circuitry can be adversely affected by therapeutic radiation. However, the published clinical data are sparse regarding the safety of radiotherapy delivery to patients with artificial pacemakers. Despite the potential risk of life threatening complications, there are no national guidelines and most radiotherapy departments have no formal clinical risk management strategy in place. A literature review was performed to assess the risks involved in irradiating patients with pacemakers and to identify strategies, which minimise the risk of pacemaker malfunction. Recommendations for radiotherapy departments are made. CONCLUSION: Modern multi-programmable pacemakers are very sensitive to therapeutic megavoltage irradiation. There is no safe radiation threshold for megavoltage radiation. The low energy kilovoltage X-rays used for radiotherapy simulation cause no pacemaker malfunction. Megavoltage radiation can be safely delivered to patients with cardiac pacemakers provided direct irradiation of pacemakers is avoided, adequate monitoring is done during and after irradiation, and the dose to the pacemaker generator is kept below 2 Gy. Close liaison with cardiologists and a pacemaker clinic is essential and radiotherapy departments should have protocols in place to identify and care for cancer patients with pacemakers.

Equipment Failure↗
PubMed2005

The use of denial in an ethnically diverse British cancer population: a cross-sectional study.

A total of 82 Asian and 117 randomly selected white Caucasian patients at the Leicestershire Cancer Centre were assessed using measures of coping and adaption to cancer. On the Mental Adjustment to Cancer (MAC) scale, Asian patients were more fatalistic (P < 0.0001) and had more significant hopeless/helpless scores (P = 0.007). The two ethnic groups answered the three questions thought to assess denial differently. Caucasians were more likely not to dwell on their illness (73 vs 55.5%, P < 0.0001) and agree with the statement 'I have difficulty believing this is happening to me' (73 vs 60.5%, P < 0.0001). However, Asian patients were more likely to agree with the statement 'I don't really believe I have cancer' (48.2 vs 31.3%, P = 0.019). Within both groups there was an association with denial and anxious preoccupation (P < 0.001). On the Hospital Anxiety and Depression (HAD) scale, there was no difference in anxiety scores between either sexes or between the Asian and Caucasian groups. However, Asian patients were more depressed (P = 0.001). Although denial was significantly related to the presence of both depression (P < 0.0001) and anxiety (P = 0.001) in the entire patient population, there were different predictors of denial in each subgroup. On multiple regression analysis depression was linked with denial in Caucasians, whereas Fighting Spirit (minus helplessness/hopelessness) was linked with denial in Asian patients. There are definite differences in coping styles in British cancer patients according to ethnicity. While significant numbers in both groups employ denial in some form, Caucasian patients appear to adapt to the psychological pressures of cancer more successfully than Asian patients at a particular point in time. Further work is required to elucidate longitudinal relationships between denial and adaption to cancer.

Adaptation, Psychological↗
PubMed2005

Concomitant chemoradiotherapy for muscle-invasive bladder cancer: the way forward for bladder preservation?

Muscle-invasive bladder cancer is a common malignancy with a high mortality rate. Despite ongoing debates about the optimal primary intervention, radical cystectomy remains the cornerstone of first-line therapy in many institutions. Over the past decade, bladder-preserving strategies involving transurethral resection (TUR), chemotherapy and radiotherapy have evolved. However, the advantage of these approaches over radiation treatment as monotherapy has yet to be fully evaluated. In other tumour models, most notably cervical and anal cancer, radiation and chemotherapy delivered concomitantly have resulted in significant survival advantages. Here, we consider the potential value of this approach in the treatment of invasive bladder cancer. Concomitant chemoradiotherapy is currently the mainstay of several bladder-preserving programmes reported in the medical literature. Overall, local control and survival rates compare favourably with contemporary cystectomy series; however, difficulties in drawing valid conclusions are highlighted. Concomitant chemoradiotherapy may have a role in the management of certain patient subgroups, and the debate should remain open. Further large-scale randomised trials are needed, and information regarding bladder function and quality of life after treatment is lacking at present. The importance of close follow-up and prompt salvage cystectomy is emphasised.

Antineoplastic Agents↗
PubMed2004

Information needs of Asian and White British cancer patients and their families in Leicestershire: a cross-sectional survey.

The aim of this questionnaire survey was to find the information needs of British Asian cancer patients. An additional objective was to find the extent of family involvement when the patient was given the cancer diagnosis and the patients' views about information disclosure. We interviewed 82 Asian patients and 220 random white control patients. More white British patients gave positive answers to the statement 'I want as much information as possible' than Asian patients (93.1 vs 77.5%, P<or=0.001). However, 92.6% of Asian patients wanted to know if they had cancer. Many more Asians (66.2 vs 5.1%, P<0.001) indicated the general practitioner (GP) as the preferred source of information. This may be because 56% of English-speaking Asian patients would prefer to discuss their illness in their mother tongue. In Leicester, many Asian patients have Asian GPs. The vast majority of both Asian and British patients agreed that family or friends should be present when patients are given the cancer diagnosis. However, Asians were more likely to be alone (24 vs 15%, P=0.008) when told they have had cancer. The majority of patients (both white British and Asian) want to control the disclosure of information to relatives and friends and would like to be present at doctor/family meetings.

Adolescent↗
PubMed2004

Concomitant hydroxyurea plus radiotherapy versus radiotherapy for carcinoma of the uterine cervix: a systematic review.

We identified eight randomised control trials of hydroxyurea and radiation versus radiotherapy alone (six published in full and two abstracts). Most concluded that outcomes were improved by use of hydroxyurea. However, methodological problems associated with these trials included small sample size, a large number of patient exclusions post randomisation, differing outcome definitions, subgroup analyses of already small numbers of patients and questionable rules for censoring, particularly a failure to include treatment related deaths in the survival analysis. All but two studies were of less than 50 patients. Patients were excluded from some analyses for treatment related reasons. The exclusion of such patients undoubtedly altered the conclusions of the studies. Even if there was a survival advantage attributed to hydroxyurea, overall survival was somewhat poor. We found the evidence regarding the use of hydroxyurea and radiotherapy to be inadequate for assessing its role in the treatment of cervical cancer.

Antineoplastic Agents↗
PubMed2004

Phase II trial of Oxaliplatin and 5-Fluorouracil/Leucovorin combination in epithelial ovarian carcinoma relapsing within 2 years of platinum-based therapy.

OBJECTIVE: To evaluate the efficacy and toxicity of Oxaliplatin and 5-Fluorouracil (5-FU)/Leucovorin (LV) combination in ovarian cancer relapsing within 2 years of prior platinum-based chemotherapy in a phase II trial. METHODS: Eligible patients had at least one prior platinum-based chemotherapy regimen, elevated CA-125 > or = 60 IU/l, radiological evidence of disease progression and adequate hepatic, renal and bone marrow function. Patients with raised CA-125 levels alone as marker of disease relapse were not eligible. Oxaliplatin (85 mg/m(2)) was given on day 1, and 5-Fluorouracil (370 mg/m(2)) and Leucovorin (30 mg) was given on days 1 and 8 of a 14-day cycle. RESULTS: Twenty-seven patients were enrolled. The median age was 57 years (range 42-74 years). The median platinum-free interval (PFI) was 5 months (range 0-17 months) with only 30% of patients being platinum sensitive (PFI > 6 months). Six patients (22%) had two prior regimens of chemotherapy. A total of 191 cycles were administered (median 7; range 2-12). All patients were evaluable for toxicity. The following grade 3/4 toxicities were noted: anemia 4%; neutropenia 15%; thrombocytopenia 11%; neurotoxicity 8%; lethargy 4%; diarrhea 4%; hypokalemia 11%; hypomagnesemia 11%. Among 27 enrolled patients, 20 patients were evaluable for response by WHO criteria and 25 patients were evaluable by Rustin's CA-125 criteria. The overall response rate (RR) by WHO criteria was 30% (95% CI: 15- 52) [three complete responses (CRs) and three partial responses (PRs)]. The CA-125 response rate was 56% (95% CI: 37-73). Significantly, a 25% (95% CI: 9-53) radiological and a 50% (95% CI: 28-72) CA-125 response rate were noted in platinum resistant patients (PFI < 6 months). The median response duration was 4 months (range 3-12) and the median overall survival was 10 months. CONCLUSION: Oxaliplatin and 5-Fluorouracil/Leucovorin combination has a good safety profile and is active in platinum-pretreated advanced epithelial ovarian cancer.

Adult↗
PubMed2003

Measurements using the alkaline comet assay predict bladder cancer cell radiosensitivity.

In the UK, the two main treatments of invasive bladder cancer are radiotherapy or cystectomy. However, approximately 50% of patients undergoing radiotherapy fail to respond. If tumour radiosensitivity could be predicted in advance, it may be possible to improve control rates significantly by selecting for radiotherapy those patients whose tumours are radiosensitive. Additionally, patients who would benefit from surgery would be identified earlier. The alkaline comet assay (ACA) is a sensitive method for the detection of DNA strand break damage in cells. In the present study, using six bladder cancer cell lines of differing radiosensitivities, cell survival was compared to the manifestation of radiogenic DNA damage as assessed by ACA. For all the cell lines, the extent of comet formation strongly correlates with cell killing (R2>0.96), with a greater response being noted in radiosensitive cells. In repair studies, measures of residual damage correlate with survival fraction at 2 Gy (R2>0.96), but for only five of the cell lines. Finally, cells from human bladder tumour biopsies reveal a wide range of predicted radiosensitivies as determined by ACA. Overall, these studies demonstrate ACA to be a good predictive measure of bladder cancer cell radiosensitivity at low dose, with potential clinical application.

Carcinoma, Transitional Cell↗
PubMed2003

Completion of the audit cycle: standardised nurse-led information for patients.

BACKGROUND: It is increasingly accepted that patients want information about their proposed treatment, and that provision of such information may alleviate fear and may improve the process of obtaining informed consent. It is not yet clear what form such information should take. OBJECTIVE: Based on differences shown previously between patients receiving standard treatment and those in clinical trials, a system of routine appointments with a chemotherapy nurse at least one day before the patient offered consent to treatment was established for all patients receiving chemotherapy in Leicestershire, at which time patients were given standardised written information regarding outpatient chemotherapy and specific drugs. METHOD: In order to complete the audit cycle, the previous questionnaire study was repeated. RESULTS: From 160 questionnaires distributed, 131 complete replies were received. Compared with the previous audit, a significantly higher proportion of patients receiving standard chemotherapy remembered being given written information about chemotherapy from a nurse before starting their treatment and remembered signing a consent form. The significant difference in feelings of involvement in the decision to have chemotherapy between patients receiving standard chemotherapy and those in clinical trials detected in the previous audit was no longer detectable, suggesting the clinical effectiveness of the intervention performed. CONCLUSION: Implementation of nurse-led appointments with provision of standardised information before formal consent being taken should be studied further for its potential to improve patients' involvement in medical decision making.

Clinical Trials as Topic↗
PubMed2002

Analgesia for pelvic brachytherapy.

Pelvic brachytherapy presents the anaesthetist with numerous challenges. Patients vary from highly distressed young adults, to the elderly with coincidental disease severe enough to preclude surgery. The painful radioactive implants remain in place for a number of days. Treatment in isolated rooms reduces radiation exposure to staff, but makes close postoperative monitoring difficult, so the analgesic technique should involve minimum risk to the patient. Although there is very little published evidence of specific analgesic techniques in this area, knowledge of these problems allows the anaesthetist to select appropriate systemic analgesics and regional blocks to provide safe and effective pain relief.

Analgesia↗
PubMed2002

New World leishmaniasis from Spain.

A 69 year old man living in Spain contracted mucocutaneous leishmaniasis involving the nose. The infecting organism was Leishmania infantum, which only rarely causes the New World form of the disease. The source of infection was probably a neighbour's dog. The patient began treatment with liposomal amphotericin B but died of pneumonia two months later.

Amphotericin B↗
PubMed2001

Involving patients in treatment decisions: can we learn from clinical trials?

The delivery of information to patients with cancer is a primary responsibility of health professionals and it may improve patients' satisfaction with their involvement in treatment decisions. Clinical trials often involve more written and verbal information for patients. All patients who were receiving chemotherapy in Leicestershire during a 2-week period were asked to complete a questionnaire. The responses of clinical trial and non-trial patients were compared. Clinical trial patients were significantly more likely to have been informed about alternative treatment options and to feel that they had taken part in the decision to undergo chemotherapy. They were also significantly more likely to have received written and verbal information about diagnosis and treatment from a hospital nurse, and were more willing to approach a nurse with future questions. If greater patient participation in treatment decisions is advocated, more written and verbal information and closer involvement of hospital nurses should be considered for all forms of chemotherapy.

Adult↗