Biomedical subjects

R A'Hern

Publications and source records attributed to R A'Hern.

At least 37 records · Page 2Linked to original sources

PubMed2001

A phase II study to establish the efficacy and toxicity of sodium valproate in patients with cancer-related neuropathic pain.

The efficacy and toxicity of sodium valproate for cancer-related neuropathic pain was evaluated in a phase II study at this cancer center. Twenty-five patients entered the study over a 13 month period. Pain was assessed using a pain scale based on the Brief Pain Inventory at days 0, 8 and 15. Nineteen patients completed the two week study period, one patient discontinued treatment because of toxicity, and five discontinued because of progressive disease. The most frequently observed side effects were drowsiness, unsteadiness, nausea, and decreased appetite. Response was defined as a decrease in pain score in the absence of increased need for analgesic medication. The response rate for average pain at day 15 in assessable patients was 55.6% (30.8-78.5%, 95% CI), but response rates varied considerably depending on the mode of analysis. Baseline efficacy data have been gained on which to base future comparative studies against antidepressants.

Adult↗

PubMed2001

Fatigue in patients with cancers of the breast or prostate undergoing radical radiotherapy.

To determine the prevalence, severity, and correlates of fatigue among patients with cancers of the prostate or breast receiving high dose radiotherapy with curative intent, a prospective, questionnaire-based study evaluated a convenience sample of 62 patients who were about to start a course of radiotherapy. Patients were assessed immediately prior to treatment, and again within a week of finishing. Fatigue was assessed using the Fatigue Severity Scale (FSS) and the Bidimensional Fatigue Scale (BFS). Quality of life was assessed using the European Organisation for Research and Treatment of Cancer 30-item Quality of Life Questionnaire (EORTC QLQc30). Psychological distress was assessed using the Hospital Anxiety and Depression Scale (HADS). Personality Traits were assessed using the Eysenck Personality Inventory (EPI). Fatigue severity increased significantly on 3 out of the 5 assessment instruments used. Radiotherapy was associated with a decline in global quality of life, role, cognitive and social functioning, and an increase in nausea/vomiting, pain, insomnia, diarrhea, and financial difficulty. At baseline, 39% of the variation in fatigue scores among the patients could be explained by a combination of measures of their global quality of life and physical functioning. A combination of fatigue and anxiety scores at baseline was able to predict 54% of the variation in fatigue scores at the completion of radiotherapy. These data indicate that fatigue is a significant problem for patients receiving radical radiotherapy, although its severity is relatively modest.

Adult↗

PubMed2001

The incidence of breast cancer from screening women according to predicted family history risk: Does annual clinical examination add to mammography?

In breast cancer, mutations of predisposition genes such as BRCA-1/2 and other genes as yet uncharacterised are manifest in up to 10% of cases. Although the prior probability of the presence of a breast cancer predisposing gene can be calculated for individual women, there is no published evidence to justify predicted risk as a selection criteria for screening. This study aims to define which patient groups with a significant family history should be screened, and whether clinical examination is necessary in addition to mammography. The Claus model was used to predict breast cancer risk in women with a family history. Women were divided into two groups according to their predicted risk: group I consisted of women at standard risk (lifetime risk less than 1:6) and group II with moderate/high risk (lifetime risk greater than or equal to 1:6). Women were cancer-free at the point of entry, and screening consisted of annual clinical examination and mammography from the age of 35 years. This study consisted of 1500 women in group I and 1078 in group II. The period of observation was 5902.0 and 4327.8 women years, respectively. A total of 31 cancers were detected, 12 in group I and 19 in group II. The median age at diagnosis in group II was 45 years (range 26-66 years) compared with 54.5 years (range 38-63 years) in group I (P=0.03). The relative risk of developing breast cancer in group II was 2.6 (95% confidence interval (CI) 1.2-5.8). When compared with breast cancer incidence in the normal population, the standardised incidence ratio in group II was significantly higher at 2.8 (95% CI: 1.7-4.2). The standardised incidence ratio of women in group I was similar to that of the general population (1.1 (95% CI: 0.6-1.8)). A total of 26/31 (84%) cancers detected were palpable, of which 14 (54%) were not visible on mammography. Approximately one-third of all palpable cancers were detected at routine follow-up. Mammography correctly identified 17/31 cancers (55%), but 29% of these were not palpable. Family history screening programmes are effective and women should be selected for screening according to predicted risk. The younger age of diagnosis in group II justifies screening from an earlier age using both annual clinical examination and mammography.

Adult↗

PubMed2001

Outcome and predictive factors of local recurrence and distant metastases following primary surgical treatment of high-grade malignant phyllodes tumours of the breast.

AIM: High-grade malignant phyllodes tumour (MPT) is a rare but aggressive breast malignancy and forms approximately 25% of all phyllodes tumours. The aim of the study was to determine parameters that influence outcome in high-grade MPT. METHODS: This study consisted of 48 women diagnosed with high-grade MPT. All patients were treated primarily with surgery by local excision (LE, margins <1 cm), wide local excision (WLE, margins > or =1 cm) or mastectomy. Cox's regression was used for multivariate analysis of the data. RESULTS: The mean patient age was 47 (range 21-85) years and the average tumour size was 7.8 (range 1.5-20) cm. Ten patients were treated with LE, 14 with WLE and 24 with mastectomy. The median follow-up was 9 years (range 5 months-28 years). Local recurrence (LR) occurred in 19 patients (40%) at mean time of 28 (range 5-84) months after primary treatment. Distant metastasis (DM) occurred in 13 (27%) patients at average time of 25.6 (range 6-120) months. LR, subsequent metastatic spread and survival following treatment of MPT were related to tumour size and excision margins, but not to other clinical or histopathological characteristics. CONCLUSION: Tumour size and surgical margins were found to be the principal determinants of LR and DM. Complete surgical excision, by mastectomy if necessary, is important in the primary surgical treatment of high-grade MPT.

Adult↗

PubMed2001

The role of radiotherapy in the management of elevated calcitonin after surgery for medullary thyroid cancer.

Among 139 patients with medullary thyroid cancer (MTC) treated at the Royal Marsden Hospital between 1957-1998, 51 had persistently elevated calcitonin levels after initial surgery in the absence of clinically or radiologically demonstrable residual disease. Of these, 24 were treated with radiotherapy because of advanced local disease at presentation; this resulted in normalization of calcitonin in only 1 patient, although 10 remained free of clinical recurrence. Surveillance alone was used in the remaining 27 patients, of whom 8 (30%) remained free of overt disease. Local relapse rate was significantly lower after radiotherapy (29% vs. 59%) but there was no significant difference in 10-year survival between the two groups (72% vs. 60%). In view of this favorable long-term survival of patients with elevated calcitonin on observation, we cannot recommend the routine use of radiotherapy. However, it does appear to have a role in those presenting with more advanced disease to reduce the incidence of loco-regional relapse.

Adult↗

PubMed2000

Synovial sarcoma: a clinicopathologic, staging, and prognostic assessment.

PURPOSE: Synovial sarcoma (SS) is a common soft tissue sarcoma (STS) with a propensity for young adults and notable sensitivity to chemotherapy (CT). This study provides a current clinicopathologic, staging, and prognostic assessment for SS. The problems with the current American Joint Committee for Cancer (AJCC) Staging System in relation to SS are discussed. METHODS: Review of a prospective database supplemented by retrospective data. RESULTS: One hundred fifty patients were assessed; median age was 30 years and median follow-up was 52 months. Overall actuarial 5-year survival rate was 57%. Size trend, but not a cutoff of less than 5 cm versus > or = 5 cm, was a prognostic indicator (P <.001). The current AJCC/International Union Against Cancer Staging System differentiated prognosis less well than the recently proposed Royal Marsden Hospital Staging System. Age greater than 20 years at diagnosis implied worse prognosis. A local recurrence event was associated with a worse survival (P <.001). Therapeutic CT was administered to 55 patients. Eleven of 19 patients had an objective response to a combination of ifosfamide and doxorubicin. Four cases had complete response after CT. Twenty-one patients had pulmonary metastasectomy, with an actuarial 5-year survival rate of 23%. CONCLUSION: SS tends to affect young people. In this subtype of STS, size trend is the most significant influence on stage and hence survival; however, smaller SSs have an unexpectedly poor prognosis. Adequate local control may affect survival. SS is often chemosensitive, and given its poor prognosis, multicenter trials of adjuvant therapy are warranted.

Adolescent↗

PubMed2000

Are randomized trials of hormone replacement therapy in symptomatic women with breast cancer feasible?

OBJECTIVE: To evaluate the feasibility of conducting a large randomized trial of HRT in symptomatic women with early-stage breast cancer. DESIGN: Open randomized study. SETTING: Outpatient clinics at The Royal Marsden and St. George's Hospitals, London. PATIENT(S): One hundred postmenopausal women with early-stage breast cancer, experiencing vasomotor symptoms and/or vaginal dryness. INTERVENTION(S): Randomization (1:1) to HRT or no HRT for 6 months. MAIN OUTCOME MEASURE(S): Acceptance, continuance rates, and the reasons eligible women declined study entry. RESULT(S): Acceptance (38.8%) and continuance rates (>80%) were encouraging. The efficacy of HRT did not appear to be antagonized with concomitant tamoxifen. Seventy-five percent of women continued HRT after the study ended. Three women developed metastatic disease. Two used HRT. CONCLUSION(S): Despite informed consent, a national UK randomized trial of HRT should be feasible and has now been planned. Successful implementation necessitates the provision of information about HRT and the estrogen deficiency side effects of breast cancer therapy to health professionals and women with breast cancer.

Adult↗

PubMed2000

Outcome of malignant spinal cord compression at a cancer center: implications for palliative care services.

One hundred sixty-six patients presented to a cancer center with malignant spinal cord compression (SCC) proven by magnetic resonance imaging (MRI). The majority of patients (92%) were treated with radiotherapy. Changes in functional capability over time were assessed using performance (PS) and neurological status (NS). Over the course of treatment, there was no significant change in PS or NS. The median survival from confirmation of SCC was 82 days (range 1-1349 days). Survival was significantly better for those presenting with good functional status. One hundred thirteen patients (68%) were discharged from hospital; 88 (78%) were discharged home, 11% were sent to another hospital, 4% were transferred to a rehabilitation unit, and 5% went to a hospice. Fifty-three patients (32%) died before discharge. The confirmation that PS and NS have prognostic significance in the functional outcome of patients with SCC may prove helpful in decisions regarding care planning for individual patients with SCC who are discharged from hospital.

Adolescent↗

PubMed2000

Fatigue in patients with prostate cancer receiving hormone therapy.

The aim of this study was to determine the prevalence, severity and correlates of fatigue in a convenience sample of outpatients with prostate cancer prior to and following 3-months treatment with first-line hormone therapy (cyproterone acetate and goserelin). 'Severe fatigue' in the patients (n=62) was defined as a score on the Fatigue Severity Scale (FSS) greater than the 95th percentile of a group of elderly volunteers without cancer. Subjects also completed other questionnaires about fatigue and about quality of life, anxiety/depression and personality. Subjects underwent a nutritional assessment, tests of voluntary muscle function and attention. The prevalence of 'severe fatigue' at baseline was 8/58 (14%). Median FSS scores increased significantly after 3 months treatment. On multivariate analysis psychological distress explained 28% of the variance in fatigue scores. Treatment was associated with a reduction in voluntary muscle function, loss of muscle bulk, a decline in virility and potency, an improvement in pain and a reduction in nausea/vomiting. Fatigue is an important but under-recognised side-effect of hormone therapy.

Aged↗

PubMed2000

Thyroid cancer in children: the Royal Marsden Hospital experience.

The first child with well-differentiated thyroid cancer treated at the Royal Marsden Hospital presented in 1917. Since that time 30 children under the age of 16 years have been treated over a period during which many new treatments have been introduced. We have reviewed their management and outcome. The median follow-up is 22.5 years (range: 1-66). The median time to recurrence was 7 years (range: 2-44). There were events up to 44 years after presentation. The risk of recurrence was higher in children aged 10 years or younger [HR 3.45, 95% CI (1.04-11.11) P = 0.03]. Thyroid stimulating hormone (TSH) suppression was the only intervention to be shown to reduce the recurrence rate [HR 11, 95% CI (2.27-50) P = 0.0003]. The median overall survival is 53 years. The only presenting feature predictive of poorer survival was the presence of metastases (HR 28.96, 95% CI 2.51-334, P < 0.001). Patients who developed recurrence had a higher risk of death (HR 9.90, 95% CI 0.98-100, P = 0.02) and a shorter median survival of 30 years. No therapeutic intervention could be shown statistically to impact on survival. Our recommendation for treatment is total or near-total thyroidectomy for all patients and radioiodine ablation for all except those with early T stage node-negative disease aged over 10 years. Modified neck dissection is recommended for children with clinically positive neck nodes and TSH suppression for all. Follow-up with serial thyroglobulin measurement should be lifelong.

Adolescent↗

PubMed2000

A study to investigate the prevalence, severity and correlates of fatigue among patients with cancer in comparison with a control group of volunteers without cancer.

BACKGROUND: Determining the prevalence of fatigue among cancer patients is complicated by the high prevalence of fatigue symptoms in the general population. The aim of this study was to determine the prevalence, severity and correlates of fatigue among both cancer patients and control subjects without cancer. PATIENTS AND METHODS: A total of 227 cancer patients and 98 control subjects were recruited to the study. They completed a number of questionnaires about fatigue, quality of life and psychological symptoms. The majority of subjects also underwent assessment of voluntary muscle function and nutritional status. Severe fatigue in the patients was defined as a score on the Fatigue Severity Scale in excess of the 95th percentile of the control group. RESULTS: The prevalence of severe fatigue was 15% among patients with recently diagnosed breast cancer, 16% among patients with recently diagnosed prostate cancer, 50% among patients with inoperable non small cell lung cancer and 78% among patients receiving specialist inpatient palliative care. In the patients a combination of dyspnoea, psychological distress, pain, and a measure of overall disease burden accounted for 56% of the variance in fatigue scores. CONCLUSIONS: Severe fatigue is a common problem among cancer patients, particularly those with advanced disease. Fatigue is significantly associated with the severity of psychological symptoms (anxiety and depression) and with the severity of pain and dyspnoea.

Adult↗

PubMed2000

Outcome of treatment for limb and limb girdle sarcomas at the Royal Marsden Hospital.

AIMS: In this study we aimed to determine local recurrence, mortality an d amputation rates in patients presenting with limb and limb girdle soft tissue sarcomas. METHOD: A review of all 439 patients presenting with p rimary or recurrent soft tissue sarcomas of limb and limb girdle to the Royal Marsden Hospital between 1989 and 1995 was carried out. RESULTS: The local recurrence rate was 15.5% and the mortality rate was 30%, with a median follow up of 3.2 years and an overall amputation rate of 4.8%. CONCLUSION: The outcome of limb and limb girdle sarcomas in this study i s comparable to those reported elsewhere.

Amputation, Surgical↗

PubMed2000

Medullary thyroid cancer: multivariate analysis of prognostic factors influencing survival.

AIMS: The aims of this study were to assess the long-term results of treatment of medullary thyroid carcinoma (MTC) and to define prognostic factors. METHODS: Retrospective analysis of all patients diagnosed with MTC between 1949 and 1998 and treated in our unit was carried out. RESULTS: One hundred and sixty-two patients (87 females, 75 males) were identified; 52 patients (32%) had familial disease. Median follow-up was 9 years (2-20 years). The majority of patients (90%) presented with a thyroid mass or enlarged neck nodes. Total/subtotal thyroidectomy was performed in 129/18 patients respectively; 45 patients also underwent neck dissection while 52 had simple nodal excision. External beam radiotherapy (RT) was given to 76 patients with advanced disease at presentation. Overall survival was 72% at 5 years and 56% at 10 years; case-specific survival was very similar. In multivariate analysis the factors which were significant predictors of survival were age at diagnosis, extent of nodal disease, extent of surgery and metastases at presentation. RT significantly reduced local relapse in patients with ipsilateral nodal disease. CONCLUSIONS: MTC may be associated with prolonged survival; the best prognosis occurs in young patients undergoing total thyroidectomy and neck dissection. External beam RT significantly reduces local relapse in patients with limited nodal disease.

Adolescent↗

PubMed2000

Lobular carcinoma in situ of the breast is not caused by constitutional mutations in the E-cadherin gene.

Lobular carcinoma in situ (LCIS) is an unusual histological pattern of non-invasive neoplastic disease of the breast occurring predominantly in women aged between 40 and 50 years. LCIS is frequently multicentric and bilateral, and there is evidence that it is associated with an elevated familial risk of breast cancer. Although women with LCIS suffer an increased risk of invasive breast disease, this risk is moderate suggesting that LCIS may result from mutation of a gene or genes conferring a high risk of LCIS, but a lower risk of invasive breast cancer. The high frequency of somatic mutations in E-cadherin in LCIS, coupled with recent reports that germline mutations in this gene can predispose to diffuse gastric cancer, raised the possibility that constitutional E-cadherin mutations may confer susceptibility to LCIS. In order to explore this possibility we have examined a series of 65 LCIS patients for germline E-cadherin mutations. Four polymorphisms were detected but no pathogenic mutations were identified. The results indicate that E-cadherin is unlikely to act as a susceptibility gene for LCIS.

Adult↗

PubMed1999

Patient-specific mutation databases for oral cancer.

Development of databases, summarising the genetic events associated with oral squamous cell carcinoma (SCC), should increase our understanding of the molecular basis of these lesions. Additionally, databases will help establish whether different cancer subtypes show different growth characteristics, because the multistage carcinogenic process is different in the various tumour subtypes. This new knowledge may also provide new prognostic information, as these aberrations represent fundamental biological characteristics of each tumour. To assess the value of incorporating the results from loss of heterozygosity (LOH) analysis into patient-specific mutation databases, we have carried out microsatellite analysis with 52 polymorphic markers at 13 key chromosomal regions implicated in the pathogenesis of head and neck cancers. Altered expression of the Rb, p53 and DCC tumour suppressor genes has also been studied by immunohistology. Our results shed light on the different pathways that lead to cancer and reveal that a variety of different patterns of allelic imbalance (AI) were detected at all TNM stages, reflecting the different clinical behaviour that tumours classified as being of the same TNM stage may exhibit. Summarising the level of genetic damage as a fractional allelic loss (FAL) score and the presence of AI at 3p22-26, 3p14.3-12.1 and 9p21 was found to be a better predictor of outcome than the TNM system. This finding suggests that molecular data can be incorporated into conventional staging systems to provide more accurate prognostic information for this group of patients.

Adult↗

PubMed1999

Treatment of nondysgerminomatous ovarian germ cell tumors: an analysis of 69 cases.

BACKGROUND: Combination chemotherapy has dramatically improved the prognosis of patients with nondysgerminomatous ovarian germ cell tumors (NDOGCT). However, guidelines are needed for the identification of patients at risk of relapse. METHODS: The authors performed a retrospective analysis of women with NDOGCT managed during the period 1970-1994 at the Royal Marsden Hospital and other hospitals of the London Gynaecological Oncology Group. RESULTS: Sixty-nine women were included; their median follow-up was 5.7 years (minimum, 12 months). The median age was 21 years (range, 4-44 years), with a histology of immature teratoma (IT) for 17 patients, endodermal sinus tumor (EST) for 20 patients, and mixed tumors for 32 patients. Thirty-five patients (51%) had Stage I disease. Nine patients with Stage I tumors were observed without further therapy (six with IT and three with mixed tumors), and one relapsed. Seven patients received non-platinum-based chemotherapy, and four relapsed. A total of 52 patients were treated with platinum-based chemotherapy, with relapse free and overall survival rates of 87% (95% confidence interval [CI], 73-93%) and 84% (95% CI, 70-91%), respectively. Of these patients, relapse was seen in 0 of 9 IT patients, 1 of 25 patients with mixed tumors, and 6 of 18 EST patients. With alpha-fetoprotein (AFP) > 1000 kU/L, relapse was seen in 6 of 18 patients compared with 1 of 33 relapses with lower AFP levels. In multivariate analysis, including all patients who received chemotherapy, AFP >1000 kU/L (P = 0.001) and non-platinum-based chemotherapy (P = 0.005) were associated with relapse. When only patients given platinum-based treatment were considered, EST histology (P = 0.003) and AFP >1000 kU/L (P = 0.003) were associated with relapse in univariate analysis; however, these factors were linked. No malignant tumor was found at second-look surgery performed on 24 patients. Of 26 women assessable for fertility, 24 subsequently recommenced regular menstrual function, and 11 patients had pregnancies. CONCLUSIONS: Platinum-based chemotherapy has been confirmed to be effective in the management of patients with NDOGCT. Relapses were principally seen among patients with AFP >1000 kU/L or pure EST histology. Efforts to improve outcome need to focus on patients with EST, whereas less intensive management strategies may be appropriate for some patients with IT.

Adolescent↗

PubMed1999

Time-related effects of estrogen withdrawal on proliferation- and cell death-related events in MCF-7 xenografts.

Endocrine treatments for human breast cancer have been based largely upon the removal of estrogenic stimuli. The regression of tumors after estrogen deprivation has generally been characterized as being due to reduced proliferation but more recently has been recognized to also involve increased apoptosis. The aim of our experiments was to define the associated changes in certain proliferation- and cell death-related biological parameters after hormone withdrawal from estrogen-dependent MCF-7 xenografts in athymic nude mice using immunohistochemical techniques. The baseline estrogen receptor (ER) level of this MCF-7 xenograft was relatively low (average H score 23) but it was strongly Bcl-2-, PgR- and pS2-positive, indicating the functional integrity of estrogen signaling. Changes in proliferation (Ki-67), apoptosis, ER, progesterone receptor (PgR), cyclin D1, p27kip1, Bcl-2 and Bax expression were assessed during the 2 weeks after estrogen deprivation. ER levels rose markedly after estrogen ablation, whereas PgR levels fell to about 10% of baseline and pS2 levels halved. The proportion of Ki-67-positive cells was unchanged after 24 hr but by day 14 had reduced by about 80%. The normal levels of cyclin D1 also reduced after estrogen withdrawal in contrast to the rapid increase in levels of cyclin-dependent kinase inhibitor p27kip1. This latter increase appeared to occur in advance of the changes in Ki-67. The proportion of apoptotic cells increased from a mean 1.5% at baseline to 2.9% after 3 days and 4.7% after 14 days. There were reductions in both Bcl-2 and Bax staining but these appeared to be greater for Bcl-2, effectively decreasing the Bcl-2/Bax ratio. Our results provide a framework for the use of these parameters as intermediate markers in comparisons of hormonal agents for human breast cancer treatment.

Animals↗

PubMed1999

Multicentre randomised controlled trial of nursing intervention for breathlessness in patients with lung cancer.

OBJECTIVE: To evaluate the effectiveness of nursing intervention for breathlessness in patients with lung cancer. DESIGN: Patients diagnosed with lung cancer participated in a multicentre randomised controlled trial where they either attended a nursing clinic offering intervention for their breathlessness or received best supportive care. The intervention consisted of a range of strategies combining breathing control, activity pacing, relaxation techniques, and psychosocial support. Best supportive care involved receiving standard management and treatment available for breathlessness, and breathing assessments. Participants completed a range of self assessment questionnaires at baseline, 4 weeks, and 8 weeks. SETTING: Nursing clinics within 6 hospital settings in the United Kingdom. PARTICIPANTS: 119 patients diagnosed with small cell or non-small cell lung cancer or with mesothelioma who had completed first line treatment for their disease and reported breathlessness. OUTCOME MEASURES: Visual analogue scales measuring distress due to breathlessness, breathlessness at best and worst, WHO performance status scale, hospital anxiety and depression scale, and Rotterdam symptom checklist. RESULTS: The intervention group improved significantly at 8 weeks in 5 of the 11 items assessed: breathlessness at best, WHO performance status, levels of depression, and two Rotterdam symptom checklist measures (physical symptom distress and breathlessness) and showed slight improvement in 3 of the remaining 6 items. CONCLUSION: Most patients who completed the study had a poor prognosis, and breathlessness was typically a symptom of their deteriorating condition. Patients who attended nursing clinics and received the breathlessness intervention experienced improvements in breathlessness, performance status, and physical and emotional states relative to control patients.

Anxiety↗