• Facial paediatric desmoid fibromatosis: a case series, literature review and management algorithm.

      Wilks, D J; Mowatt, David J; Merchant, W; Liddington, M I; Department of Plastic and Reconstructive Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK. (2012-05)
      Desmoid fibromatosis (also known as infantile or aggressive fibromatosis) is a rare soft tissue tumour that is occasionally seen in children. Although histologically benign, its growth pattern is highly aggressive often showing invasion of surrounding musculature and bone. Frequently found in cosmetically sensitive areas, complete excision can present a challenging problem. However, incomplete surgical excision is associated with high recurrence rates and although the disease responds to chemo and radiotherapy, both carry significant risks in young children. The management of four paediatric desmoid fibromatoses occurring in the midface is discussed. The recent and pertinent literature is comprehensively reviewed and an algorithm for the management of paediatric desmoid fibromatoses is proposed.
    • Facilitating reproductive choices: the impact of health services on the experiences of young women with breast cancer.

      Lee, Rebecca J; Wakefield, Ann; Foy, Sharon; Howell, Sacha J; Wardley, Andrew M; Armstrong, Anne C; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK. (2010-09-02)
      Objective: Chemotherapy and hormone treatments carry significant implications on the fertility of young women with breast cancer. Increasingly, nulliparous women experience fertility dilemmas due to rising survival rates and pregnancy delay. This qualitative study investigated women's responses to being told that treatments affected their fertility and how their interactions with health services impacted on their experiences.Methods: Twenty-four women under 40 years participated in three focus groups using a flexible interview structure. Data were analysed using content analysis and participants subsequently member checked the themes generated.Results: The priority for most women was survival, although women without children were more willing to take risks. Many women felt that pregnancy after breast cancer and methods of egg harvesting carried a significant risk to survival and fears appeared to be increased by conflicting advice from health professionals. Overall, the women felt the cancer, its treatment options and the health service itself had each robbed them of choice. Hence, with hindsight, many said they would have welcomed an open and honest discussion with a fertility expert to maximise their options.Conclusions: Young women with breast cancer face complex decisions regarding their fertility and treatment options. Survival remains the priority for the majority of women. Although there is a paucity of evidence concerning many fertility issues, it is essential that available options and any potential risks are discussed in a coherent, objective fashion. Early referral to specialist fertility services that provide clear, cohesive advice can aid informed decision making. Copyright © 2010 John Wiley & Sons, Ltd.
    • Factors affecting local regrowth after watch and wait for patients with a clinical complete response following chemoradiotherapy in rectal cancer (InterCoRe consortium): an individual participant data meta-analysis.

      Chadi, S; Malcomson, Lee; Ensor, J; Riley, R; Vaccaro, C; Rossi, G; Daniels, I; Smart, N; Osborne, M; Beets, G; et al. (2018-10-11)
      In patients with rectal cancer who achieve clinical complete response after neoadjuvant chemoradiotherapy, watch and wait is a novel management strategy with potential to avoid major surgery. Study-level meta-analyses have reported wide variation in the proportion of patients with local regrowth. We did an individual participant data meta-analysis to investigate factors affecting occurrence of local regrowth.
    • Factors affecting remission and survival in patients with advanced Hodgkin's disease treated with MVPP.

      Wagstaff, John; Steward, William P; Jones, Mary; Deakin, David P; Todd, Ian D; Wilkinson, Peter M; Scarffe, J Howard; Harris, Martin; Crowther, Derek; CRC, University of Manchester Department of Medical Oncology, Manchester, U.K. (1986)
      One hundred and fourteen patients with clinical or pathological stages IIIB and IV Hodgkin's disease have been treated with MVPP chemotherapy followed by radiotherapy to sites of previously bulky disease. The minimum follow-up is 2 years with a median of 5 years. The overall remission rate was 92 per cent with 74 per cent achieving CR. A discriminant analysis showed that the presence of bulky disease was the only independent factor that predicted a lower chance of CR (66 per cent vs 82 per cent, P = 0.045). The 5-year survival was 70 per cent overall and 85 per cent for CR patients. A Cox multivariate analysis demonstrated that stage III disease, age less than 36 years and female sex were all variables which independently predicted a more favourable prognosis in terms of overall survival. However, a similar analysis for survival of CR patients showed that age less than 36 years and the absence of bulky disease were the only two factors to independently predict a more favourable outcome. Of 14 patients who did not receive the chemotherapy according to protocol 5 have relapsed compared to 7 of 70 who did. A Cox analysis confirmed that this variable was the only one of significant prognostic import in predicting relapse-free survival. Using the Cox analyses we have been able to devise a scoring system which accurately predicts the outcome for these patients. This model may be useful in determining which patients have a worse prognosis following treatment with MVPP thus allowing more intensive therapy to be given to such patients while minimising treatment for those with favourable features.
    • Factors affecting the radiation dose to the lens of the eye during cardiac catheterization procedures.

      Pratt, T A; Shaw, A J; North Western Medical Physics Department, Christie Hospital, Withington, Manchester, UK. (1993-04)
      Concern has been expressed about the relatively high radiation doses to the lens of the eye received by the operator during cardiac catheterization studies. A study was undertaken to assess the occupational doses received by cardiologists and to examine the factors that affect the individual's eye dose. Eighteen cardiologists working in five catheterization laboratories at three centres were included in the study. Their eye doses, workload and individual study details were monitored at each centre. Operating dose rates and scattered radiation were also measured for each unit to compare equipment performance. The study demonstrated that the relationships between the cardiologist's eye dose and factors such as the dose efficiency of the X-ray equipment, scattered dose rates, examination protocols and workload are complex and vary from centre to centre. Because of these variations general workload limits may be inaccurate and should only be used for general guidance when no direct measurements are available. Such limits should be verified by local measurements as soon as is practical.
    • Factors associated with recurrence and survival length following relapse in patients with neuroblastoma.

      Basta, N; Halliday, G; Makin, Guy W J; Birch, J; Feltbower, R; Bown, N; Elliott, M; Moreno, L; Barone, G; Pearson, A; et al. (2016-10-25)
      Despite therapeutic advances, survival following relapse for neuroblastoma patients remains poor. We investigated clinical and biological factors associated with length of progression-free and overall survival following relapse in UK neuroblastoma patients.
    • Factors determining ultra-short-term survival and the commencement of active treatment in high-grade serous ovarian cancer: a case comparison study

      Hawarden, A.; Russell, B.; Gee, M. E.; Skayali, F.; Clamp, Andrew R; Crosbie, E. J.; Edmondson, R. J.; Division of Cancer Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, St Mary's Hospital, Research Floor, Oxford Road, Manchester, M13 9WL, (2021)
      Background: Despite improvements in median survival some patients with advanced ovarian cancer die within 100 days of diagnosis; the reasons for which remain poorly understood. Here we investigate if ultra short-term survival can be explained by patient characteristics or treatment pathways. Methods: A nested case comparison study was used to examine differences between patients with high grade serous ovarian/fallopian tube cancer who died within 100 days (n = 28) compared to a comparison group of patients matched for histology and including any survival greater than 100 days (n = 134). Results: Cases and comparison patients had similar ages, BMI, ACE-27, deprivation indices, and distribution of disease on CT. There were no significant delays in time to diagnosis or treatment (p = 0.68) between the groups. However, cases had lower serum albumin, haemoglobin and higher platelet counts than matched comparison patients (p < 0.0001) and a worse performance score (P = 0.006). Conclusion: Patients who die rapidly after a diagnosis of ovarian cancer are only slightly older and have similar pre treatment frailty compared to patients whose survival approaches the median. However they do appear to undergo greater physiological compromise as a result of their disease.
    • Factors influencing microculture of leukaemia cells.

      Balkwill, F; Pindar, A; Crowther, Derek; Department of Medical Oncology, St. Bartholomew's Hospital, West Smithfield, London, EC1 (1974)
    • Factors influencing salvage cystectomy results.

      Osborn, D E; Honan, R P; Palmer, Michael K; Barnard, R J; McIntyre, D; Pointon, R C S; Department of Urology, Christie Hospital, Manchester (1982-04)
      Analysis of 86 patients who underwent salvage cystectomy following a radical course of radiotherapy for bladder cancer and 37 patients who underwent primary cystectomy has shown a greater survival for women than men. The following factors were associated with a significant deterioration in survival: 1. Age at time of cystectomy: post-operative mortality and tumour recurrence are greater over the age of 70. 2. Non-function of one kidney on IVU. 3. Grade 3 tumour on cystectomy specimen. 4. pT3 or pT4 tumour on cystectomy specimen.
    • Factors influencing the desire for long-term growth hormone replacement in adults.

      Holmes, Sarah J; Shalet, Stephen M; Department of Endocrinology, Christie Hospital NHS Trust, Manchester, UK. (1995-08)
      OBJECTIVE: Growth hormone replacement in adults may be considered beneficial by clinicians, but patients may not perceive any benefits. The purpose of this study was to determine whether there were any factors which influenced whether an adult wished to continue on long-term GH replacement after taking part in a study of GH replacement. DESIGN: A 12-month study (double-blind placebo controlled for the first 6 months and open for the second 6 months) of GH replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter) in adults. PATIENTS: Sixty-three adults (27 men, 36 women, aged 34.9 +/- 1.4 (mean +/- SE, range 20.1-59.5) years) with GH deficiency (peak serum GH response to provocative testing less than 10 mU/l) who entered a 12-month study of GH replacement. Thirty patients (48%) wished to continue on GH replacement and 33 patients (52%) did not wish to continue on GH replacement after the study. MEASUREMENTS: Biochemical, anthropometric and demographic characteristics, and well-being, were compared in those patients who wished to continue on long-term GH replacement and in those who did not. In the two groups of patients the age, height, weight, body mass index, serum insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and IGF-I age matched standard deviation score (SDS) were compared at entry into the study, and changes in IGF-I, IGFBP-3 and IGF-I SDS were compared after 6 months of GH replacement. The patients were compared according to pretreatment peak serum GH response to provocative testing, sex, estimated duration of GH deficiency, whether GH deficiency was of childhood or adult onset, presence or absence of additional pituitary hormone deficiencies, underlying pathological disorder, previous therapeutic interventions, employment status, marital status and living arrangement, and according to development of side-effects of GH replacement and the requirement for reduction in dose of GH because of side-effects during the study. Scores on two questionnaire measures of well-being or distress, the Nottingham Health Profile (NHP) and the Psychological General Well-Being Schedule (PGWBS), were compared at entry into the study in the two groups, as were change in scores on these questionnaires after 6 months of GH replacement. RESULTS: Those who continued on GH replacement tended to have a greater severity of GH deficiency (median peak serum GH concentration 0.7 vs 2.3 mU/l, P = 0.06), tended to have greater distress in terms of energy (NHP, P = 0.06) and vitality (PGWBS, P = 0.06) at entry into the study and showed an improvement in energy during the study compared with no change in those who did not wish to continue on GH replacement (NHP, P = 0.06). CONCLUSION: Those adults who wished to continue on GH replacement tended to have a greater severity of GH deficiency, to experience more distress in terms of energy and vitality at entry into the study and to experience an improvement in energy after 6 months treatment with GH.
    • Factors influencing timely management of stage I non-small cell lung cancer (NSCLC) in the multidisciplinary team meeting (MDT).

      Queen, Z.; Bayman, Neil A; Chan, Clara; Marti, Kalena; Rammohan, K.; Shah, R.; Sheikh, Hamid Y; Sundar, R.; Webster, I.; Taggart, S.; et al. (2018-01)
    • Factors predicting long-term survival after T-cell depleted reduced intensity allogeneic stem cell transplantation for acute myeloid leukemia.

      Craddock, Charles; Nagra, Sandeep; Peniket, Andrew; Brookes, Cassandra; Buckley, Laura; Nikolousis, Emmanouil; Duncan, Nick; Tauro, Sudhir; Yin, John A; Liakopoulou, Effie F; et al. (2010-06)
      BACKGROUND: Reduced intensity conditioning regimens permit the delivery of a potentially curative graft-versus-leukemia effect in older patients with acute myeloid leukemia. Although T-cell depletion is increasingly used to reduce the risk of graft-versus-host disease its impact on the graft-versus-leukemia effect and long-term outcome post-transplant is unknown. DESIGN AND METHODS: We have characterized pre- and post-transplant factors determining overall survival in 168 patients with acute myeloid leukemia transplanted using an alemtuzumab based reduced intensity conditioning regimen with a median duration of follow-up of 37 months. RESULTS: The 3-year overall survival for patients transplanted in CR1 or CR2/CR3 was 50% (95% CI, 38% to 62%) and 44% (95% CI, 31% to 56%), respectively compared to 15% (95% CI, 2% to 36%) for patients with relapsed/refractory disease. Multivariate analysis demonstrated that both survival and disease relapse were influenced by status at transplant (P=0.008) and presentation cytogenetics (P=0.01). Increased exposure to cyclosporine A (CsA) in the first 21 days post-transplant was associated with an increased relapse risk (P<0.0001) and decreased overall survival (P<0.0001). CONCLUSIONS: Disease stage, presentation karyotype and post-transplant CsA exposure are important predictors of outcome in patients undergoing a T-cell depleted reduced intensity conditioning allograft for acute myeloid leukemia. These data confirm the presence of a potent graft-versus-leukemia effect after a T-cell depleted reduced intensity conditioning allograft in acute myeloid leukemia and identify CsA exposure as a manipulable determinant of outcome in this setting.
    • Factors which affect the CFU-GM content of the peripheral blood haemopoietic progenitor cell harvests in patients with acute myeloid leukaemia.

      Jowitt, Simon N; Chang, James; Morgenstern, Godfrey R; Howe, T; Ryder, W David J; Testa, Nydia G; Scarffe, J Howard; Department of Haematological Oncology, Christie Hospital NHS Trust, Manchester. (1998-03)
      Autologous peripheral blood haemopoietic stem cells (PBSC) were harvested from 30 patients with de novo acute leukaemia, 29 of whom had entered remission following standard chemotherapy. Correlation of CD34+ cells/kg to CFU-GM/kg in the harvests was good (correlation coefficient = 0.72, P < 0.001). We demonstrated significant associations between the CFU-GM content of the harvest and the following: time to platelets >50 x 10(9)/l post final induction course (P < 0.001), days to harvest from day 1 of intensification/mobilization (correlation coefficient = -0.73, P < 0.001), platelets >20 x 10(9)/l at time of harvest (P = 0.02), time to WBC >1.0 x 10(9)/l post intensification/mobilization (correlation coefficient = -0.70, P < 0.001), and WBC on day of harvest (correlation coefficient = 0.60, P < 0.001). In contrast, we found no relationship between the CFU-GM content of the harvest and patient age up to 65 years, presence of absence of coexistent features of trilineage myelodysplasia at diagnosis, number of induction courses to remission or total number of courses of chemotherapy prior to intensification/mobilization. Haemopoietic recovery after reinfusion of PBSC was highly correlated to the number of CFU-GM infused (neutrophils >0.5 x 10(9)/l rs = -0.72, P = 0.001; platelets >20 x 10(9)/l unsupported rs = -0.71, P = 0.001). Our results show that the number of induction courses received, and thus exposure to cytotoxic agents received, made no significant difference to subsequent CFU-GM harvest content. We collected superior harvests from those patients with faster platelet recovery following mobilization therapy. We also found that faster platelet recovery following the final induction therapy was a better predictor of the CFU-GM harvest following mobilization than was the neutrophil recovery following final induction.
    • Failure of antibody response to polysaccharide antigen in treated panhypopituitary adults.

      Mukherjee, Annice; Helbert, M; Ryder, W David J; Borrow, R; Davis, Julian R E; Shalet, Stephen M; Department of Endocrinology, Christie Hospital, Manchester, UK. annice.mukherjee@srht.nhs.uk (2009-05)
      Although pituitary hormones are known to affect immune function, treated hypopituitarism is not a recognized cause of immune deficiency in humans. We set out to assess integrity of baseline and stimulated immune function in severely hypopituitary adults. Twenty-one panhypopituitary adults (group 1), on stable pituitary replacement including growth hormone, and 12 healthy volunteers (group 2) were studied. Lymphocyte subsets, pneumococcal antibody levels pre- and 1 month after polysaccharide vaccination, T cell numbers and in-vitro interferon (IFN)-gamma response were studied. There were no significant differences in T cell numbers or IFN-gamma secretion. B cell numbers were lower in group 1, especially those with low prolactin levels. Independent of this finding, nine of 21 patients in this group had low antibody response to polysaccharide antigen. This was most striking in those with low insulin-like growth factor 1 levels and appeared to be independent of the use of anti-convulsants or corticosteroid replacement. Significant humoral immune deficiency is seen in panhypopituitarism and may contribute to morbidity.
    • Failure of lithium to reduce period of neutropenia during induction therapy of acute myeloid leukemia.

      Scarffe, J Howard; Chang, James; CRC Department of Medical Oncology, Christie Hospital, Manchester, U.K. (1989)
      Fifty-four patients treated with daunorubicin, cytosine arabinoside and thioquanine for acute myeloid leukemia were randomly assigned to receive oral lithium carbonate 1200 mg daily or no lithium. The duration of neutropenia (less than 0.5 x 10(9)/L) was similar between controls (median 22.5 days) and patients treated with lithium (median 24 days). The number of remissions, relapse-free survival and survival were similar for the lithium treated and control groups of patients. There was no apparent clinical efficacy in the use of lithium to reduce the period of neutropenia in patients undergoing remission induction therapy for acute myeloid leukemia.
    • Failure to preserve fertility in patients with Hodgkin's disease.

      Waxman, J; Ahmed, R; Smith, David B; Wrigley, P; Gregory, W; Shalet, Stephen M; Crowther, Derek; Rees, L; Besser, G; Malpas, J; et al. (1987)
      The hypothesis that the "down-regulated" gonad is less vulnerable to the effects of cytotoxic chemotherapy for advanced Hodgkin's disease has been investigated. Thirty men and eighteen women were randomly allocated to receive an agonist analogue of gonadotrophin-releasing hormone prior to, and for the duration of, cytotoxic chemotherapy. Buserelin (d-Ser-[TBU]6 LHRH ethylamide) was prescribed in two different dosage schedules to twenty men, and in a single dosage schedule to eight women. A standard gonadotrophin-releasing hormone test (GnRH 100 micrograms) was performed 1 week prior to and on day 1 of each cycle of chemotherapy. In all patients peak luteinizing hormone responses to GnRH were suppressed throughout treatment. The higher of the two dosage schedules used in the men caused more effective suppression of luteinizing hormone, and both regimens led to an initial suppression of peak follicle-stimulating hormone responses to GnRH, which was not maintained. At follow-up assessment up to 3 years from the completion of treatment, all men treated with buserelin were profoundly oligospermic and four of the eight women were amenorrhoeic. All ten male controls were profoundly oligospermic, and six of nine female controls were amenorrhoeic. In the dosages and schedules investigated, buserelin was ineffective in conserving fertility.
    • Failure-free survival and radiotherapy in patients with newly diagnosed nonmetastatic prostate cancer: data from patients in the control arm of the STAMPEDE trial.

      James, N; Spears, M; Clarke, Noel W; Dearnaley, D; Mason, M; Parker, C; Ritchie, A; Russell, J; Schiavone, F; Attard, G; et al. (2015-11-25)
      The natural history of patients with newly diagnosed high-risk nonmetastatic (M0) prostate cancer receiving hormone therapy (HT) either alone or with standard-of-care radiotherapy (RT) is not well documented. Furthermore, no clinical trial has assessed the role of RT in patients with node-positive (N+) M0 disease. The STAMPEDE Trial includes such individuals, allowing an exploratory multivariate analysis of the impact of radical RT.
    • FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity

      Timbrell, Simon; Aglan, Hosam; Cramer, Angela; Foden, P.; Weaver, D.; Pachter, J.; Kilgallon, Aoife; Clarke, Robert B; Farnie, Gillian; Bundred, Nigel J; et al. (2021)
      Cancer stem-like cells (CSC) contribute to therapy resistance and recurrence. Focal adhesion kinase (FAK) has a role in CSC regulation. We determined the effect of FAK inhibition on breast CSC activity alone and in combination with adjuvant therapies. FAK inhibition reduced CSC activity and self-renewal across all molecular subtypes in primary human breast cancer samples. Combined FAK and paclitaxel reduced self-renewal in triple negative cell lines. An invasive breast cancer cohort confirmed high FAK expression correlated with increased risk of recurrence and reduced survival. Co-expression of FAK and CSC markers was associated with the poorest prognosis, identifying a high-risk patient population. Combined FAK and paclitaxel treatment reduced tumour size, Ki67, ex-vivo mammospheres and ALDH+ expression in two triple negative patient derived Xenograft (PDX) models. Combined treatment reduced tumour initiation in a limiting dilution re-implantation PDX model. Combined FAK inhibition with adjuvant therapy has the potential to improve breast cancer survival.
    • False family history of breast cancer in the family cancer clinic.

      Kerr, Bronwyn; Foulkes, William D; Cade, D; Hadfield, L; Hopwood, Penelope; Serruya, Corinne; Hoare, E; Narod, Steven A; Evans, D Gareth R; Department of Medical Genetics, St Mary's Hospital, Manchester. (1998-08)
      AIMS: Awareness of hereditary breast and ovarian cancer in both the general public and the medical profession is increasing. Individuals who may be at risk on the basis of a family history are requesting risk determination and appropriate management in a variety of settings. Risk determination relies largely on pedigree analysis and epidemiological data. METHODS: We describe five individuals presenting in the family cancer or genetic counselling clinic where a factitious family or personal history led to erroneous risk estimation. Common factors in these families are a history of benign breast disease, poor communication within families, long survival with early onset or bilateral disease, a lack of detailed knowledge of the illness and treatment in close relatives and inconsistencies in the history in repeated consultations.
    • False-negative MRI breast screening in high-risk women.

      Maxwell, A; Lim, Y; Hurley, E; Evans, D; Howell, Anthony; Gadde, S; Nightingale Centre, University Hospital of South Manchester, Manchester, UK (2016-12-05)
      To determine the frequency of and reasons for false-negative breast magnetic resonance imaging (MRI) examinations in high-risk women undergoing annual screening.