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Biomedical subjects

R A'Hern

Publications and source records attributed to R A'Hern.

At least 19 recordsLinked to original sources
PubMed2006

Clinical outcome and service implications of screening women at increased breast cancer risk from a family history.

INTRODUCTION: The value of special screening for women at moderate breast cancer risk with a family history of breast cancer remains controversial. Little is known about recall rates, false negative outcomes and the impact on clinical service. Despite this, surveillance programmes within breast units have been established in the United Kingdom. PATIENTS AND METHODS: In our institution, screening of women at moderate (lifetime risk, 17-30%) and high risk (>30%) consisted of annual clinical examination and mammography from the age of 35 years. The active study period ran for four months and each patient was followed through a further screening cycle (whole study period), providing information on interval cancers and detection at the subsequent screen. RESULTS: One thousand one hundred and thirty-two women attended for their incident screen: 137 at high risk, 803 at moderate risk and 192 at standard risk. The median age at cancer diagnosis in the moderate risk group was 54 (range, 45-68) years and the high-risk group 51 (46-52) years, compared to 63 (45-69) years in the standard risk group. Seven cancers were diagnosed during the four-month active study period. Two patients were diagnosed with interval cancers and eight at the next screen, giving a cancer incidence in the whole study period of 17/1132 (1.5%). Thirteen patients had invasive cancer and four had ductal carcinoma in situ (DCIS) The median invasive tumour size was 15 had (range, 7-28)mm and the median DCIS size was 4 (2-30)mm. 10/13 (76.9%) invasive cancers were < or =20mm and 2/13 patients (15.4%) with invasive cancer were lymph node positive. The sensitivity and specificity of mammography were 85.7% and 98.8%, respectively. The mammogram recall rate was 27.6 per 1000. The benign to malignant surgery ratio was 8:17. CONCLUSION: Screening women at increased breast cancer risk is effective. Early detection and recall rates are comparable to that of older women attending the British National Breast Screening Programme.

Adult↗
PubMed2006

Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, progesterone receptor, EGF receptor and HER2 status.

BACKGROUND: Most women with oestrogen receptor (ER) positive primary breast cancer receive adjuvant tamoxifen after surgery. The measurement of tumour biomarkers should allow better selection of patients for such treatment or for therapies such as aromatase inhibitors. PATIENTS AND METHODS: Histopathological blocks of primary breast cancer patients who had been randomized to receive 2-years tamoxifen or no adjuvant therapy in two mature randomised clinical trials were retrieved. Immunohistochemical staining for ER, progesterone receptor (PgR), HER2 and epidermal growth factor receptor (EGFR) was undertaken. The primary endpoint was relapse free survival. RESULTS: 813 patients were included in the study. Benefit from tamoxifen was seen in ER-positive patients [Relative risk (rr) 0.77, ci 0.63-0.93]. ER-negative patients also showed a strong trend to benefit from tamoxifen (rr 0.73, ci 0.52-1.02) which was largely confined to the PgR-positive group. Amongst the ER-positive group, PgR-positive and PgR-negative patients showed similar benefit (rr 0.81; ci 0.65-1.02 and 0.70; ci 0.49-0.99, respectively). Patients positive for HER2 did not benefit significantly (rr 1.14; ci 0.75-1.73) but this group was small. CONCLUSIONS: Measurement of PgR status in ER-negative patients defines a group of patients that benefit from tamoxifen but would be excluded from tamoxifen therapy on the basis of ER status alone. The data are consistent with HER2 positive tumours being resistant to tamoxifen.

Adult↗
PubMed2006

Randomized phase II study of GM-CSF to reduce mucositis caused by accelerated radiotherapy of laryngeal cancer.

Acute mucositis is dose-limiting in many accelerated radiotherapy schedules for head and neck cancer. Cytokines may be one means of reducing the severity of mucositis. A study was designed to assess the effect of subcutaneous molgramostin (granulocyte-macrophage colony stimulating factor; GM-CSF) injections on acute radiation morbidity in patients undergoing accelerated radiotherapy for laryngeal cancer. A prospective, randomized, observer-blind, controlled trial was conducted in 29 patients who were to receive radical radiotherapy over 3 weeks for early stage laryngeal cancer. Patients were randomized to receive 150 microg (approximately 2 microg kg(-1)) GM-CSF subcutaneously once daily for 14 days after the second week of radiotherapy, or no GM-CSF. Patients were assessed weekly for grade of mucositis, skin reactions and related parameters. The severity of mucositis was reduced in the GM-CSF arm (p<0.05). No other end-points reached statistical significance. Two patients failed to complete their courses of GM-CSF. Three developed influenza type symptoms and in one an allergic reaction was noted. There was no difference in tumour control rates. Subcutaneous GM-CSF reduced the severity of mucositis in patients undergoing accelerated radiotherapy. Injections were well tolerated. Further studies of cytokines are warranted, to assess the feasibility of increasing the total doses of accelerated radiotherapy given, with the aim of improving tumour cure rates.

Aged↗
PubMed2005

Association between polymorphisms of the GPX1 gene and second primary tumours after index squamous cell cancer of the head and neck.

We investigated the association between genetic polymorphisms in GPX1 gene amongst patients who had index squamous cell carcinoma (SCCHN) and a second primary tumour (SPT) after a primary SCCHN in a case-control study. GPX1 genotypes were determined for 61 patients with SPT and for 259 control subjects by a PCR technique using a fluorescent-labelled primer. Analysis was by an ABI automated fluorescent sequencer. The associations between specific genotypes and the development of SPT were examined by logistic regression. A significant difference was found between the control group and the SPT cases in allele frequencies of GPX1 ALA( *)6 and ALA( *)7 (p(trend)=0.04). These results suggest that polymorphisms in the GPX1 gene may be a marker for SPT development and further studies are indicated.

Adult↗
PubMed2005

An open study of methotrimeprazine in the management of nausea and vomiting in patients with advanced cancer.

INTRODUCTION: Nausea and vomiting are distressing symptoms affecting between 20% and 70% of patients with advanced cancer. Methotrimeprazine is a phenothiazine antipsychotic used in palliative care for the management of terminal agitation and nausea/vomiting but there is only anecdotal evidence to support its use in palliative care. AIM: To establish whether nausea/vomiting in palliative care patients is improved by the administration of low-dose methotrimeprazine. METHODS: Patients with advanced malignancy were entered at different treatment levels according to symptom severity. The dose was altered according to response (minimum dose 6.25 mg daily po, maximum 25 mg by 24-h subcutaneous infusion). Symptoms and side effects were recorded daily from 0 (baseline) to day 5 using a four-point scale. Any improvement in nausea/vomiting score was taken as a response. RESULTS: Sixty-five patients were entered. The cause of nausea and vomiting was multifactorial in the majority of patients, 35/65 (54%). As expected in a study of patients with poor performance status, the attrition rate was high. Of 53 patients evaluable for response at day 2, 33 (62%) showed some improvement in nausea or vomiting. At day 5, improvement was seen in 20/34 (58%). There was no significant change in "side effects" from baseline with time. CONCLUSION: These results suggest that methotrimeprazine has antiemetic activity.

Adult↗
PubMed2005

Continued axillary sampling is unnecessary and provides no further information to sentinel node biopsy in staging breast cancer.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) has become increasingly accepted as a diagnostic method to stage the axilla in breast cancer, selecting women with a positive sentinel node for completion axillary clearance. As SLNB became established, many surgeons supplemented SLNB to sample a minimum of four lymph nodes, on the assumption that the four-node technique is supported by randomised trial data. We hypothesised that the practice of undirected sampling to supplement SLNB adds little information to the status of the residual axilla. METHODS: One hundred and sixty-five patients with early breast cancer were studied. Following successful identification of the sentinel node, 84 women had completion axillary dissection and 81 women had an axillary sample with at least four nodes available for pathological assessment. RESULTS: Following successful identification of the sentinel node in 165 patients, the false negative rate (FNR) was 2/44=4.5% (95% CI 0.6-15.5), sensitivity 42/44=95.5% (84.5-99.4) and negative predictive value (NPV) 121/123=98.4% (94.2-99.8). In the axillary dissection cohort, the FNR was 2/26=7.7% (0.9-25.1), sensitivity 24/26=92.3% (74.9-99.1) and NPV 58/60=96.7% (88.5-100). In the axillary sample group, the FNR was 0/18=0% (0-18.5), sensitivity 18/18=100% (81.5-100) and NPV 63/63=100% (94.3-100). The SLNB was the only positive node in 12/26 (46.2%) in the axillary dissection group and 10/18 (55.6%) in the axillary sampling group. There was no patient in the axillary sampling group where the sample node was positive and the sentinel node negative. CONCLUSION: Once SLNB is validated within the multidisciplinary unit, undirected sampling of the axilla following identification of the sentinel node(s) is unnecessary. The additional sampling of non-sentinel nodes has no role to play either in the assessment of a potential false negative SLNB nor as predictive information on the status of the residual axillary nodes.

Adult↗
PubMed2004

A phase II feasibility study of carboplatin followed by sequential weekly paclitaxel and gemcitabine as first-line treatment for ovarian cancer.

A total of 53 women with chemotherapy-naïve stage Ic-IV ovarian cancer were treated with four cycles of carboplatin area under the curve 7 every 3 weeks, followed by four cycles of paclitaxel 70 mg m(-2) (days 1, 8, and 15) and gemcitabine 1000 mg m(-2) (days 1 and 8) every 3 weeks. In all, 37 (70%) had stage III/IV disease, with 22 (42%) having tumour >2 cm; 38 patients (72%) completed all planned treatment; 27 of the 32 (84%) patients with radiologically evaluable disease had partial or complete responses; and 30 of the 39 patients (77%) with elevated cancer antigen (CA) 125 had a greater than 75% fall in this value. At a median follow-up of 28 months, 31 patients had relapsed with a median progression-free survival of 19.5 months. In total, 79% of patients were alive at 2 years. Common Toxicity Criteria grade 3/4 haematological toxicity, predominantly neutropenia, was seen in 57% of the patients. A certain degree of pulmonary toxicity was observed; eight patients had symptomatic breathlessness, +/- decreased diffusing capacity of the lung for carbon monoxide, and interstitial chest X-ray changes during the weekly phase. In all cases, this toxicity was reversible. No significant neurotoxicity was seen. This regimen is generally well tolerated with encouraging efficacy. However, the observation of pulmonary toxicity, potentially a feature of the weekly taxane-gemcitabine regimen, was of some concern. Alternative schedules, including 3-weekly taxanes, are currently being evaluated.

Adult↗
PubMed2004

Serum vascular endothelial growth factor as a tumour marker in soft tissue sarcoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent tumour-produced angiogenic factor. In this study serum levels of VEGF were measured before treatment and during follow-up in patients undergoing primary treatment for suspected soft tissue sarcoma (STS) to assess the value of serum VEGF as a tumour marker. METHODS: Between April 2001 and September 2002, serum VEGF levels were analysed prospectively in 144 patients undergoing primary treatment (surgery, 123; cytotoxic chemotherapy, ten; oral imatinib, eight; radiotherapy, three) for suspected soft tissue sarcoma. Serum VEGF was measured by immunoassay before treatment, in the immediate postoperative interval in patients undergoing surgery, and during follow-up. Serum VEGF concentrations were also measured in 15 healthy volunteers. RESULTS: Median pretreatment serum VEGF levels were significantly raised in patients with grade 2 and grade 3 sarcomas compared with concentrations in patients with benign lesions (413 and 467 versus 233 pg/ml respectively; P=0.007 and P=0.003 respectively). In patients with tumours that had a high level of VEGF expression before treatment, follow-up measurements reflected disease status after treatment. CONCLUSION: Serum VEGF expression correlated with grade in soft tissue sarcoma and reflected response to treatment.

Antineoplastic Agents↗
PubMed2004

Aggressive fibromatosis of the abdominal wall, limbs and limb girdles.

BACKGROUND: Aggressive fibromatosis (AF) is a rare soft-tissue tumour. It is histologically benign but locally aggressive and destructive. Surgery is the mainstay of treatment. This was a review of patients treated at the Royal Marsden Hospital between 1986 and 2003. METHODS: Records of patients with abdominal wall (23) and limb or limb girdle (86) AF were studied to determine patient, tumour and treatment characteristics and outcome. Children and patients with intra-abdominal AF were excluded. The data were analysed by Cox regression to calculate univariate hazard ratios. RESULTS: Twenty-one (19.3 per cent) of 109 patients developed recurrence after a median follow-up of 39 months. Recurrence did not correlate with surgical margin or any other variable. CONCLUSION: Wide excisional, function-preserving surgery is the goal in treatment of AF. Surgery for recurrent disease is often curative. Tumours are frequently irresectable at presentation and an initial period of expectant observation is advisable because growth arrest is a common feature of the disease.

Abdominal Neoplasms↗
PubMed2004

Clinical presentation and long-term outcome of pure myoepithelial carcinoma of the breast.

INTRODUCTION: Pure myoepithelial carcinoma of the breast is a rare tumour of controversial histogenesis. Little is known about its natural history and long-term outcome following treatment. METHODS: All patients with pure myoepithelial carcinoma treated at our institution between 1970 and 2001 were studied with respect to pathological features, outcome and prognosis. RESULTS: Six patients were identified. The median age was 60 (40-66) years and median follow-up was 34.5 months (range 14-76) months. Four tumours were T1 and one was T2 (one tumour size unknown). There were two moderately differentiated and three well-differentiated tumours (grade could not be assessed in one patient). Oestrogen and progesterone receptor could be assessed in five patients and all were negative. Primary treatment was wide local excision with clear radial margins. Lymph node assessment was negative in all patients. One patient received adjuvant radiotherapy. Three patients developed local recurrence at 15, 38 and 50 months and two patients developed distant metastasis at 30 and 79 months. The local recurrences were treated by further excision but two patients developed distant metastasis at intervals of 15 and 26 months, respectively. Two patients have died of the disease and four remain well. The 2-year and 5-year survival was 88% (SE, 6) and 55% (SE, 16), respectively. Large tumour size is a prognostic indicator of poor outcome. CONCLUSION: Pure myoepithelial carcinoma of the breast adopts an aggressive clinical course with an outcome comparable to poorly differentiated adenocarcinoma of the breast.

Adult↗
PubMed2003

Mucosal malignant melanoma of the head and neck: the Marsden experience over half a century.

We reviewed patients treated at The Royal Marsden Hospital for mucosal malignant melanoma of the head and neck between 1945 and 1996. The analysis included 89 patients, and this study is the largest so far reported from a single institution in the literature. The overall 5-year survival rate for the patient population was 23% (95% confidence interval: 14-33) and the 10-year survival rate was 12%, (6-21%). The only significant predictor of survival was the tumour stage at presentation. Radical local excision was the only treatment that provided a chance of cure. Adding radiotherapy to surgery in tumours that could be radically excised did not confer any statistically significant advantage in reducing local recurrence or improving survival.

Adult↗
PubMed2003

Buttock soft tissue sarcoma: clinical features, treatment, and prognosis.

BACKGROUND: Primary buttock soft tissue sarcomas in adults are common entities that have been infrequently reported (three clinical series and isolated case reports). We present our experience of buttock sarcomas to better characterize and define the natural history of this condition. METHODS: Buttock tumors occurring in adults (>16 years) between January 1990 and January 2002 were identified from the Royal Marsden Hospital's Sarcoma Unit prospective database. RESULTS: Seventy-three buttock sarcomas were evaluated and treated at the Royal Marsden Hospital during this period. Liposarcoma (n = 19), leiomyosarcoma (n = 13), and synovial sarcoma (n = 9) were the most frequent histological types. There were 8 T1 and 61 T2 tumors, and size was not available in 4 patients. Most tumors (n = 64) were located deep to the deep fascia. There were 15 grade 1, 20 grade 2, and 37 grade 3 tumors, and grade was not available in 1 patient. There were 29 tumors contained within the gluteus maximus. Wide excision was performed in 50 patients. Local recurrence and distant metastasis occurred in 15 and 35 patients with a median time of 18 and 8 months, respectively. The rate of local recurrence at 2 years was 20.9% (SE, 6.8%). The 2-year overall and disease-free survival rates were 64.1% (SE, 6.7%) and 48.5% (SE, 6.4%), respectively. CONCLUSIONS: Buttock sarcomas present special surgical difficulties because of proximity of the sciatic nerve and the ability of tumors at this site to extend into the pelvis and perineum. Size and grade of the tumor were independent predictors for disease-free and overall survival.

Adolescent↗
PubMed2002

Is there a dose response relationship for clodronate in the treatment of tumour induced hypercalcaemia?

Eighty-six patients with tumour induced hypercalcaemia were randomised to 600, 900, 1200 or 1500 mg of intravenous clodronate, according to post hydration serum calcium levels. Sixty-seven were evaluable for response. The overall response rate was 49.3% (95% CI: 36.8-61.8) with no significant difference in response rates, i.e. achievement of normocalcaemia at days 6-9 (corrected serum calcium < or =2.6 mmol l(-1)) across all groups.

Adult↗
PubMed2001

No germline mutations in CDKN2A (p16) in patients with squamous cell cancer of the head and neck and second primary tumours.

There is increasing evidence that predisposition to some cancers has a genetic component. There is a high incidence of loss of heterozygosity on chromosome 9, in the region of tumour suppressor gene, CDKN2A (also known as p16), in sporadic squamous cell cancer of the head and neck (SCCHN). To investigate the possibility that CDKN2A may be involved in the inherited susceptibility to SCCHN, the 3 coding exons of CDKN2A were sequenced in 40 patients who had developed a second primary cancer after an index squamous cell cancer of the head and neck. No mutations were found and we conclude that CDKN2A mutations do not play a major role in cancer susceptibility in this group.

Aged↗
PubMed2001

Contribution of germline MLH1 and MSH2 mutations to lobular carcinoma in situ of the breast.

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 suggesting a genetic basis to the disease. The high frequency of microsatellite instability in lobular breast cancers, coupled with increased risk of breast cancer associated with germline mismatch repair gene mutations raises the possibility that mutations MSH2 or MLH1 might confer susceptibility to LCIS. To explore this possibility we have examined a series of 71 LCIS patients for germline MSH2 and MLH1 mutations. No mutations were detected in MSH2. Two sequence variants were identified in MLH1. The first was a CTT-->CAT substitution, codon 607 (exon 16) changing leucine to histidine. The other mutation detected in MLH1 was a TAC-->TAA substitution codon 750 (exon 19) creating a stop codon, predicted to generate a truncated protein. These findings suggest that mutations in MLH1 may underlie a subset of LCIS cases.

Adaptor Proteins, Signal Transducing↗
PubMed2001

The psychosocial impact of bilateral prophylactic mastectomy: prospective study using questionnaires and semistructured interviews.

OBJECTIVES: To investigate the psychosocial impact of bilateral prophylactic mastectomy for women with increased risk of breast cancer and to identify, preoperatively, risk factors for postoperative distress. DESIGN: Prospective study using interviews and questionnaire assessments. SETTING: Participants' homes throughout the United Kingdom. PARTICIPANTS: 143 women with increased risk of developing breast cancer who were offered bilateral prophylactic mastectomy and who accepted or declined the surgery; a further 11 were offered surgery but deferred making a decision. MAIN OUTCOME MEASURES: Psychological and sexual morbidity. RESULTS: Psychological morbidity decreased significantly over time for the 79 women who chose to have surgery (accepters): 58% (41/71) preoperatively v 41% (29/71) 6 months postoperatively (difference in percentages 17%, 95% confidence interval 2% to 32%; P=0.04) and 60% (39/65) preoperatively v 29% (19/65) 18 months postoperatively (31%, 15% to 47%; P<0.001). Psychological morbidity in the 64 women who declined surgery (decliners) did not decrease significantly: 57% (31/54) at baseline v 43% (23/54) at 6 months (14%, 0% to 29%; P=0.08) and 57% (29/52) at baseline v 41% (21/52) at 18 months (16%; -2% to 33%; P=0.11). Greater than normal proneness to anxiety was more common in the decliners than in the accepters: 78% (45/58) v 56% (41/73) (22%, 6% to 38%; P=0.006). Accepters were more likely than decliners to believe it inevitable that they would develop breast cancer (32% (24/74) v 10% (6/58) (difference in percentages 22%, 9% to 35%; P=0.003)), and decliners were more likely to believe that screening could help (92% (55/60) v 74% (55/74) (18%, 5% to 31%; P=0.007)). Level of sexual discomfort and degree of sexual pleasure did not change significantly over time in either of the two groups. CONCLUSIONS: Bilateral prophylactic mastectomy may provide psychological benefits in women with a high risk of developing breast cancer.

Adaptation, Psychological↗
PubMed2001

Prognostic index for extremity soft tissue sarcomas with isolated local recurrence.

BACKGROUND: Local recurrence occurs in 10% to 20% of patients with extremity soft tissue sarcomas despite optimal treatment. The association of local recurrence with subsequent survival is controversial and conflicting. There is a need for a staging system to predict outcome in this subset of patients and also to plan optimal treatment, including adjuvant systemic therapy. METHODS: Data collected from 110 patients with locally recurrent extremity soft tissue sarcomas were studied. The influence of clinical and pathologic factors on local recurrence, distant metastasis, and disease-specific survival were analyzed by univariate and multivariate techniques. RESULTS: Of the 110 patients who presented with local recurrence, 92 had an isolated local recurrence and 18 had prior or concomitant distant metastases. The 5-year disease-specific survival for all patients was 63% and for those with isolated local recurrence, it was 69%. Histologic grade, malignant fibrous histiocytoma histology, pathologic margins, previous local recurrence, and prior radiotherapy were independent prognostic factors for subsequent local recurrence. Tumor size, histologic grade, and time to local recurrence were independent prognostic factors for distant metastasis and disease-specific survival. A prognostic index was calculated by assigning a score of 1 to 3 for each of the three independent prognostic factors for survival and added to give the prognostic index for each patient. As the prognostic index increased from 3 to 9, there was a progressive increase in the hazard ratios and a corresponding deterioration in survival. The patients were then categorized into three prognostic groups based on the hazard ratios for disease specific survival. The differences in the survival curves were highly statistically significant (P < .0001). CONCLUSIONS: Tumor size, histologic grade, and time to local recurrence are the primary determinants of distant metastases and survival in locally recurrent extremity soft tissue sarcomas. The impact of local recurrence on survival varies considerably. The nature of the local recurrence, rather than its presence per se, is a more useful guide to prognosis. We propose a simple staging system based on size, grade, and time to recurrence that correlates extremely well with prognosis and may serve as a guide to make therapeutic decisions in patients with locally recurrent extremity soft tissue sarcomas.

Adolescent↗