Publications (26)54.77 Total impact
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Article: Oral bisphosphonates, concurrent thoracic radiotherapy and oesophagitis.
Clinical Oncology 06/2009; 21(8):636-7. · 2.07 Impact Factor -
Article: Intensity-modulated radiotherapy planning from limited anatomical information: is Sim-CT sufficient for planning women with breast cancer receiving intensity-modulated radiotherapy?
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ABSTRACT: To investigate intensity-modulated radiotherapy (IMRT) plans for women with carcinoma of the breast, using a small number of Sim-CT slices, thus avoiding changing the patient's position and potential problems with CT capacity. Ten CT scans of women with breast cancer were obtained for use in the study. IMRT plans based on an open tangent pair and additional top-up segment fields were created using the full CT scan, and represented the gold standard treatment plan for comparison purposes. Five-slice CT simulator scans were artificially created by omitting intermediate slices from the full CT scans. Additionally, the intermediate CT slices were recreated via interpolation of the five slices using a standard interpolation algorithm. IMRT plans were created in the same way as for the full CT scans. To allow a suitable plan comparison to be made, the beam segments and monitor units were transferred to the full CT scans, and the dose distribution calculated. The interpolated five-slice plans showed no significant difference in the volume of tissue receiving dose outside the range 95-105%, compared with the IMRT plans created using the full CT data set (1.3 +/- 2.2%, P = 0.092). In contrast, the discrete slice CT simulator plans increased by 6.3 +/- 5.4%, P = 0.0054, showing a statistically significant difference in the dose distribution produced and a clinically inferior plan. Plans created using five discrete slice CT scans were inferior to full CT-derived IMRT treatment plans, and are therefore not acceptable for IMRT. However, interpolating five CT simulator slices provides adequate anatomical information to produce comparable IMRT plans to those created by full CT scans of the patient. This allows the introduction of IMRT for this patient group without the need to change treatment position to accommodate CT scanning.Clinical Oncology 09/2005; 17(5):343-51. · 2.07 Impact Factor -
Article: Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer.
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ABSTRACT: Trastuzumab is an effective treatment for patients with metastatic breast cancer (MBC) that overexpresses HER-2. A high incidence of brain metastases (BM) has been noted in patients receiving trastuzumab. A retrospective chart review was conducted of 100 patients commencing trastuzumab for metastatic breast cancer from July 1999 to December 2002, at the Christie Hospital. Seven patients were excluded; five patients developed central nervous system metastases prior to starting trastuzumab, and inadequate data were available for two. Out of the remaining 93 patients, 23 (25%) have developed BM to date. In all, 46 patients have died, and of these 18 (39%) have been diagnosed with BM prior to death. Of the 23 patients developing BM, 18 (78%) were hormone receptor negative and 18 (78%) had visceral disease. Univariate analysis showed a significant association between the development of cerebral disease and both hormone receptor status and the presence of visceral disease. In conclusion, a high proportion of patients with MBC treated with trastuzumab develop symptomatic cerebral metastases. HER-2-positive breast cancer may have a predilection for the brain, or trastuzumab therapy may change the disease pattern by prolonging survival. New strategies to address this problem require investigation in this group of patients.British Journal of Cancer 09/2004; 91(4):639-43. · 5.04 Impact Factor -
Article: Association of transforming growth factor beta-1 single nucleotide polymorphisms with radiation-induced damage to normal tissues in breast cancer patients.
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ABSTRACT: To investigate whether transforming growth factor beta-1 (TGFbeta1) single nucleotide polymorphisms were associated with the susceptibility of breast cancer patients to severe radiation-induced normal tissue damage. PCR-RFLP assays were performed for TGFbeta1 gene polymorphisms on DNA obtained from 103 breast cancer patients who received radiotherapy. The G-800A, C-509T, T+869C and G+915C polymorphic sites were examined, and genotype and allele frequencies of two subgroups of patients were calculated and compared. The less prevalent -509T and +869C alleles were significantly associated with a subgroup of patients who developed severe radiation-induced normal tissue fibrosis (n=15) when compared with those who did not (n=88) (odds ratio=3.4, p=0.0036, and 2.37, p=0.035, respectively). Furthermore, patients with the -509TT or +869CC genotypes were between seven and 15 times more likely to develop severe fibrosis. These findings imply a role for the -509T and +869C alleles in the pathobiological mechanisms underlying susceptibility to radiation-induced fibrosis. Their predictive value would be limited to patients who are -509TT or +869CC, but if "fibrosis-associated" polymorphic sites in other genes could be identified, it may be possible to detect fibrosis prone individuals before radiotherapy with greater certainty.International Journal of Radiation Biology 03/2003; 79(2):137-43. · 2.28 Impact Factor -
Article: Arm pain due to subclavian artery stenosis after radiotherapy for recurrent breast cancer.
Clinical Oncology 03/2003; 15(1):37. · 2.07 Impact Factor -
Article: Local recurrence of breast cancer following surgery and radiotherapy: incidence and outcome.
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ABSTRACT: Local recurrence of cancer in the treated breast following breast-conserving surgery and radiotherapy occurs in a minority of patients, but can represent a significant clinical problem. The impact of local relapse on the subsequent course of the disease is disputed. The aim of this retrospective review was to identify the rate and prognostic factors for breast recurrence and to determine the subsequent outcome. The case notes of 2159 patients treated between 1989 and 1992 were reviewed. Actuarial local relapse rate was 6.3% at 5 years. Factors predictive for recurrence on multivariate analysis were age (P<0.001), status of excision margins (P=0.019), and pathological UICC stage (P=0.01). One hundred and sixty-one patients developed local recurrence in the treated breast of whom 101 were treated with further surgery. The 5-year cancer-specific survival of this group was comparable with that of the patients who remained free of breast relapse (82 vs. 88%) but subsequently fell to 61 vs. 80% at 8 years (P<0.001). Sixty patients were unable to have salvage surgery; their cancer-specific survival was much worse than that of patients with operable recurrences at 33% at 5 years and 13% at 8 years. Eighty-three patients (4% of the original 2159 patients) had uncontrolled local disease at time of death or last follow-up. The prognosis of patients who developed recurrence within 2 years of their initial treatment was inferior to those who developed recurrences after 4 years (cancer-specific survival 5 years post-recurrence 23 vs. 57% P=0.008). Systemic therapy should be considered for patients with early breast recurrence in view of their inferior survival.Clinical Oncology 02/2003; 15(1):25-31. · 2.07 Impact Factor -
Article: Short report: a morbidity scoring system for Clinical Oncology practice: questionnaires produced from the LENT SOMA scoring system.
Clinical Oncology 03/2002; 14(1):68-9. · 2.07 Impact Factor -
Article: Craniospinal radiotherapy for medulloblastoma in a man with severe kyphoscoliosis.
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ABSTRACT: Medulloblastoma is an uncommon tumour in the adult population. Maximum surgical resection followed by craniospinal irradiation with a posterior fossa boost is the standard treatment. We report the case history of an adult with medulloblastoma and severe kyphoscoliosis. The unusual anatomy of the patient posed a technical challenge to the oncologist and the physicist in planning the craniospinal radiotherapy. A shaped spinal field matched to a parallel opposed pair of shaped head fields was used. The technique used in treating this patient was made possible with the use of a multileaf collimation and verification with an electronic portal imaging device. The patient remains well with no sign of relapse 4 years after treatment.Clinical Oncology 02/2001; 13(2):117-9. · 2.07 Impact Factor -
Article: Accuracy of axillary MR imaging in treated breast cancer for distinguishing between recurrent tumour and treatment effects: does intravenous Gd-DTPA enhancement help in cases of diagnostic dilemma?
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ABSTRACT: To evaluate the sensitivity and specificity of axillary magnetic resonance imaging (MRI) in symptomatic patients, who had previously been treated for breast cancer, compared with clinical outcome after a minimum of 1 year. One hundred and five patients underwent axillary MRI examinations and were diagnosed as axillary tumour, metastatic tumour, treatment effect or normal. At MRI, 48 patients had axillary tumour, 51 had metastatic tumour (37 had both), 27 had treatment effect and 22 were normal. At outcome (median follow-up, 484 days), 54 patients were positive for axillary tumour, 59 for metastatic disease (40 had both), 21 had treatment effect alone and 18 were clear. Magnetic resonance imaging showed 89% sensitivity, 100% specificity and 94% accuracy for recurrent axillary tumour, and 85% sensitivity, 98% specificity and 90% accuracy for metastatic tumour. Soft tissue plaques were the commonest axillary disease pattern seen (37). Small volume soft tissue plaques gave the most diagnostic difficulty. Non-dynamic enhancement with intravenous Gadopentetate dimeglumine (Gd-DTPA) in a subset of 34 patients improved sensitivity for axillary tumour from 40 to 74%, and improved diagnostic confidence in 11 patients (32%). Magnetic resonance imaging had a positive management impact leading to treatment alteration in 45 patients, 43 of whom had recurrent axillary and/or metastatic tumour. Tumour plaques were the commonest pattern of recurrent axillary disease. Forty-eight percent of the patients had metastatic deposits identified by MRI. Magnetic resonance imaging had excellent specificity (100%) and good sensitivity (89%) for recurrent axillary tumour compared with outcome at 1 year, which was improved by non-dynamic administration of Gd-DTPA in 32% of the subset who received it.Clinical Radiology 01/2001; 55(12):921-8. · 1.95 Impact Factor -
Article: A correlation between residual radiation-induced DNA double-strand breaks in cultured fibroblasts and late radiotherapy reactions in breast cancer patients.
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ABSTRACT: Prediction of late normal tissue reactions to radiotherapy would permit tailoring of dosage to each patient. Measurement of residual DNA double strand breaks using pulsed field gel electrophoresis (PFGE) shows promise in this field. The aim of this study was to test the predictive potential of PFGE in a group of retrospectively studied breast cancer patients. Thirty nine patients, treated uniformly for breast cancer 9-15 years previously, with excision of the tumour and radiotherapy to the breast and drainage areas, were assessed clinically using the LENT SOMA scale, and a 5-mm punch biopsy taken from the buttock. Fibroblast cell strains were established and used to study residual DNA double strand breaks, using PFGE. There were significant correlations between the DNA assay results and the fibrosis score (r(s) = 0.46; P = 0.003), the combined fibrosis and retraction score (r(s) = 0.45, P = 0.004) and the overall LENT score (r(s) = 0.43; P = 0.006). Using polychotomous logistic regression, the fibroblast DNA assay result was an independent prognostic factor for fibrosis severity. There is a relationship between residual radiation-induced DNA damage in fibroblasts and the severity of the late normal tissue damage seen in the patients from whom the cells were cultured.Radiotherapy and Oncology 05/1999; 51(1):55-65. · 5.58 Impact Factor -
Article: Lack of correlation between residual radiation-induced DNA damage, in keratinocytes assayed directly from skin, and late radiotherapy reactions in breast cancer patients.
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ABSTRACT: To study the relationship between the severity of late reactions to radiotherapy in breast cancer patients, and the extent of residual radiation-induced DNA damage, using a rapid assay of keratinocytes obtained directly from skin biopsies. A review was made of 32 patients with breast cancer, treated uniformly by radiotherapy between 1983 and 1988, following breast-conserving surgery. Their late radiotherapy reactions were scored (9-14 years post-radiotherapy) using a modified LENT SOMA scale, and a 5-mm buttock skin punch biopsy was obtained. Intact skin was irradiated at room temperature, and after allowing 24 h for repair, the tissue was disaggregated and the cells processed for pulsed field gel electrophoresis (PFGE). Residual DNA damage was expressed as the fraction of DNA released (FDR) following 150 Gy. Studies using flow cytometry on disaggregated breast skin showed that over 90% of the cells were keratinocytes. The PFGE assay was robust with low background FDRs in unirradiated skin samples (mean 3.2%) and a wide range of FDRs following irradiation from 11.5% to 26.6%. No correlation was found between the FDR at 150 Gy (FDR 150) and any of the late reaction scores or retrospective acute reaction scores. There was, however, a borderline significant correlation for family history and FDR 150 (p = 0.059). Rapid measurement of residual DNA damage in irradiated differentiated keratinocytes, the predominant cell population in skin biopsies, showed no correlation with the severity of symptomatic early or documented late reactions in a retrospectively studied group of 32 breast cancer patients.International Journal of Radiation OncologyBiologyPhysics 03/1999; 43(3):481-7. · 4.11 Impact Factor -
Article: Outcome of radiotherapy after breast conserving surgery in screen detected breast cancers.
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ABSTRACT: The treatment outcomes were reviewed for all the patients at this institute who underwent breast irradiation after breast conserving surgery in 1991. Of a total of 643 patients treated, 194 (30%) had presented with tumours detected by screening mammography. The breast was irradiated with a tangential pair of fields, giving a dose of 40 Gy in 15 fractions over 3 weeks in 97% of these patients. A boost was not used. With a median follow-up of 4.7 years, there was better cancer related survival in patients with screen detected cancers compared with those that were non-screen detected (94% versus 84% at 5 years; P = 0.002). The breast recurrence rate at 5 years was 1% for screen detected cancers compared with 6% for those that were non-screen detected (P = 0.01). Factors additional to screen detected status that were found to be significant for cancer survival were pathological stage (P = 0.03) and histological grade (P = 0.01). In a Cox multivariate analysis, only two factors were significant for breast recurrence: screen detected status (P = 0.023) and histological grade (P = 0.016). This study suggests that breast irradiation with 40 Gy given over 3 weeks after breast conserving surgery for screen detected breast cancer gives a high level of local control out to 5 years.Clinical Oncology 02/1999; 11(1):40-5. · 2.07 Impact Factor -
Article: Use of electronic portal imaging to assess cardiac irradiation in breast radiotherapy.
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ABSTRACT: An audit was performed to assess the frequency of cardiac irradiation in patients receiving radiotherapy for left-sided breast cancer. Images from an 'online' electronic portal imaging device were reviewed in patients who were treated with a tangential pair of megavoltage fields. In 169 consecutive patients treated on a Philips SL25 6 MV linear accelerator equipped with an SRI 100 imaging device, the cardiac apex was included in the radiotherapy field in 15 patients (9%). The long term sequelae of such cardiac irradiation is uncertain. The results of this audit suggest that careful treatment technique and quality control with portal imaging can minimize unnecessary cardiac irradiation in the majority of patients.Clinical Oncology 02/1997; 9(4):259-61. · 2.07 Impact Factor -
Article: Prognostic factors for breast recurrence after conservative breast surgery and radiotherapy: results from a randomised trial.
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ABSTRACT: Prognostic factors predicting for breast recurrence following breast conserving surgery and radiotherapy have been identified in a prospective randomised trial comparing two different radiotherapy techniques. The first used megavoltage radiation to encompass the whole breast and regional nodes (WF group). The second used an electron field directed to the tumour bed only (LF group). With a median follow up of 8 years survival in both groups was the same (72%). There was an increased rate of breast recurrence in the LF group: 25%, compared to the WF group: 13% (P = 0.00008), expressed in actuarial terms at 8 years. In a multivariate analysis of factors predicting for breast recurrence, once the difference in treatment technique is allowed for, only two factors were found to be significant: histological grade (P = 0.013) and lymphovascular invasion in the histological specimen (P = 0.037).Radiotherapy and Oncology 07/1996; 39(3):223-7. · 5.58 Impact Factor -
Article: Analysis of carcinoma of the endometrium treated with post operative radiotherapy.
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ABSTRACT: An audit was carried out of post-operative radiotherapy given for carcinoma of the endometrium at the Christie Hospital between the years of 1984-86. 139 patients were treated following total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). 54 patients were treated with vaginal brachytherapy alone, 55 had pelvic brick external beam irradiation and 30 patients had both external beam irradiation and vaginal brachytherapy. Overall survival was 84% at 5 years, with a 5.8% local recurrence rate. Histological grade was a prognostic factor for survival (p=0.023) and relapse (p=0.002). Tumour stage was a significant prognostic factor for survival (p=0.011), but not relapse. Survival for stage IB disease was 100% at 5 years with no local recurrence. Major treatment related morbidity was 1.4%, overall; for vaginal brachytherapy alone 0%; for external beam therapy 2%; and combined therapy 3%. Given their good prognosis, and the small but definite risk of major morbidity, patients with stage IB disease may not need postoperative external beam irradiation.International Journal of Oncology 01/1995; 6(1):265-9. · 2.40 Impact Factor -
Article: The Christie Hospital breast conservation trial: an update at 8 years from inception.
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ABSTRACT: In 1990, we published the results of a clinical trial involving 708 patients with breast carcinoma of 4 cm or less in diameter, who, following lumpectomy, were randomized to have radiotherapy to the tumour bed only (limited field, LF group) or to the whole breast and regional nodes (wide field, WF group). No adjuvant systemic therapy was prescribed. At the time the median follow-up was 37 months. We present the updated results after an extended median follow-up of 65 months. The overall survival is 72.7% and 71.2% for the LF and WF groups respectively. The actuarial breast recurrence rate (first event) is 15% (LF) versus 11% (WF) for infiltrating ductal carcinoma, whereas, for infiltrating lobular carcinoma, the recurrence rate was 34% (LF) versus 8% (WF). A high actual recurrence rate of 21% (LF) and 14% (WF) was also found for extensive ductal carcinoma in situ. It was extremely rare for medullary, mucoid or tubular carcinomas to recur. Salvage surgery was possible in 86% (LF) and 90% (WF) respectively. The recurrence rate in the breast following lumpectomy and wide field irradiation is comparable with others reported in the literature. This trial also shows the lumpectomy with limited field irradiation is feasible, albeit with a higher breast recurrence rate; the latter could be reduced by improved selection and refinement of the technique.Clinical Oncology 02/1993; 5(5):278-83. · 2.07 Impact Factor -
Article: Use of an electron beam for post-mastectomy radiotherapy: 5-year follow-up of 500 cases.
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ABSTRACT: Since 1982, the standard method of postmastectomy regional radiotherapy at the Christie Hospital has been to use a single electron field of fixed energy (8 MeV) to irradiate the chest wall, matched to a single megavoltage field (4 or 8 MV) irradiating the nodal areas in the axilla and supraclavicular fossa. (A separate parasternal field was not used.) All 500 cases treated in 1982 and 1983 with this method were reviewed (median follow-up 59 months). Four hundred and twenty-two were referred directly post-mastectomy and 78 for local recurrence after previous mastectomy. Of these, 42 were treated palliatively, and 458 with radical intent. In radical cases the given dose in both fields was 40 Gy in 15 fractions in 3 weeks. The overall survival (n = 458) was 51% (actuarial) at 5 years. At 5 years the local recurrence rate by site and UICC stage were as follows: chest wall - all Stages 17%, Stage I 4%, Stage II 13%, Stage III 26%, recurrent cases 21%; axillary recurrence - all Stages 20%, Stage I 4%, Stage II 10%, Stage III 22%, recurrent cases 39%; supraclavicular recurrences - all Stages 9%. Only one patient of the 500 treated had a parasternal recurrence. Late effects included mild telangiectasia in the electron field and asymptomatic apical lung fibrosis in the photon field. There was no match line fibrosis.Clinical Oncology 12/1991; 3(6):310-4. · 2.07 Impact Factor -
Article: The antiemetic effect of granisetron in lower hemibody radiotherapy.
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ABSTRACT: Radiotherapy-induced emesis is poorly controlled with existing antiemetics. 5-Hydroxytryptamine (5HT3) receptor antagonists are a new class of antiemetics which have been demonstrated to be effective in controlling cytotoxic-induced emesis. We have prospectively studied the antiemetic efficacy of the 5HT3 receptor antagonist granisetron in an open non-randomized efficacy and toxicity study, at two dose levels, in patients receiving lower hemibody radiotherapy for multiple bone metastases. Of the 22 patients studied, 13 patients received 20 micrograms/kg and nine patients 40 micrograms/kg of granisetron, administered as an intravenous infusion 1 h before radiotherapy. Radiotherapy was administered as a single exposure to the lower half body to a midline dose of 8 Gy. A complete response (no nausea or vomiting) was observed in 9/13 patients at the lower dose level and 6/9 patients at the higher level. No major adverse events were recorded. We conclude that granisetron is a well-tolerated and effective antiemetic agent in radiotherapy-induced emesis. Formal comparison with conventional antiemetic agents in this situation is required.Clinical Oncology 10/1991; 3(5):247-9. · 2.07 Impact Factor -
Article: The treatment of advanced seminoma with chemotherapy and radiotherapy.
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ABSTRACT: Between 1979 and 1984 thirty-seven patients were treated with combination chemotherapy for metastatic seminoma; 27 of these had relapsed following initial radiotherapy for stage I and IIA disease and 10 patients with stage IIB-IV disease received chemotherapy de novo followed by radiotherapy to sites of bulk disease. Treatment consisted of either a cis-platinum containing combination (25 patients), or cyclophosphamide and etoposide (12 patients). The overall survival of all patients at 5 years was 49%, 34 patients were assessable for response; a CR was obtained in 8 (24%) and a GPR in 19 (56%), the 5 year survival of this group being 66% at 5 years. No difference in survival was seen in relation to age, previous irradiation, serum HCG or LDH; bulk disease however, was an adverse prognostic factor. Survival was similar for both chemotherapy schedules but neutropenia and life-threatening sepsis was less with the cyclophosphamide etoposide combination.British Journal of Cancer 02/1988; 57(1):100-4. · 5.04 Impact Factor -
Article: The christie hospital breast conservation trial: An update at 8 years from inception
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ABSTRACT: In 1990, we published the results of a clinical trial involving 708 patients with breast carcinoma of 4 cm or less in diameter, who, following lumpectomy, were randomized to have radiotherapy to the tumour bed only (limited field, LF group) or to the whole breast and regional nodes (wide field, WF group). No adjuvant systemic therapy was prescribed. At the time the median follow-up was 37 months. We present the updated results after an extended median follow-up of 65 months. The overall survival is 72.7% and 71.2% for the LF and WF groups respectively. The actuarial breast recurrence rate (first event) is 15% (LF) versus 11% (WF) for infiltrating ductal carcinoma, whereas, for infiltrating lobular carcinoma, the recurrence rate was 34% (LF) versus 8% (WF). A high actual recurrence rate of 21% (LF) and 14% (WF) was also found for extensive ductal carcinoma in situ. It was extremely rare for medullary, mucoid or tubular carcinomas to recur. Salvage surgery was possible in 86% (LF) and 90% (WF) respectively. The recurrence rate in the breast following lumpectomy and wide field irradiation is comparable with others reported in the literature. This trial also shows the lumpectomy with limited field irradiation is feasible, albeit with a higher breast recurrence rate; the latter could be reduced by improved selection and refinement of the technique.Clinical Oncology.
Top co-authors
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Institutions
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2005
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The University of Manchester
Manchester, ENG, United Kingdom
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1993
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The Christie NHS Foundation Trust
Manchester, ENG, United Kingdom
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