• E-cadherin and beta-catenin are down-regulated in prostatic bone metastases.

      Bryden, A A G; Hoyland, Judith A; Freemont, Anthony J; Clarke, Noel W; Schembri Wismayer, D; George, Nicholas J; Christie and Hope Hospital, University of Manchester, UK. (2002-03)
      OBJECTIVE: To determine the E-cadherin and beta-catenin expression phenotype in untreated primary prostate cancer and corresponding bone metastases. MATERIALS AND METHODS: Paired bone metastasis and primary prostate specimens were obtained from 14 men with untreated metastatic prostate carcinoma. The tumours were histologically graded by an independent pathologist. Expression of mRNA for E-cadherin and beta-catenin was detected within the tumour cells using in-situ hybridization with a 35S-labelled cDNA probe. The expression of E-cadherin and beta-catenin were graded as uniform, heterogeneous or negative. RESULTS: The mRNA for E-cadherin was expressed in 13 of 14 primary carcinomas and 11 bone metastases; beta-catenin was expressed by 13 and nine, respectively. Of the primary tumours, nine expressed E-cadherin and beta-catenin uniformly; in contrast, all metastases had down-regulated E-cadherin and/or beta-catenin. CONCLUSIONS: The down-regulation of E-cadherin and beta-catenin are a feature of the metastatic phenotype, which may be a significant factor in the genesis of bone metastases. However, this does not appear to be reflected in the expression of these molecules in the primary tumours.
    • E-Cadherin expression in blastic plasmacytoid dendritic cell neoplasms: an unrecognized finding and potential diagnostic pitfall

      Shenjere, Patrick; Chasty, R; Chaturvedi, Anshuman; Dennis, Michael; Wiseman, Daniel H; Menasce, Lia P; Ong, A; Department of Histopathology, The Christie NHS Foundation Trust, Mancheste (2020)
      E-cadherin is expressed in hematopoietic erythroid precursors, but to our knowledge, its expression in blastic plasmacytoid dendritic cell neoplasm (BPDCN) has not been described. We report a case of BPDCN showing strong expression of E-cadherin, arising in a patient with history of primary myelofibrosis. Four more cases of BPDCN tested all showed strong expression of E-cadherin. Lack of awareness of this pattern of expression may lead to erroneous diagnosis of acute erythroid leukemia. It is increasingly becoming important to correctly identify this group of neoplasms, as approved new anti-CD123-targeted therapies are becoming available. Keywords: E-cadherin expression; acute erythroid leukemia; anti-CD123-targeted therapies; blastic plasmacytoid dendritic cell neoplasms; erroneous diagnosis; primary myelofibrosis.
    • E.O.R.T.C. phase II study of cisplatin in cyvadic-resistant soft tissue sarcoma.

      Bramwell, Vivien H C; Brugarolas, A; Mouridsen, H; Cheix, F; De Jager, F; Van Oosterom, A; Vendrik, C P; Pinedo, H; Sylvester, R; De Pauw, M; et al. (1979-12)
    • EACH: A phase II study evaluating the safety and anti-tumour activity of avelumab and cetuximab in recurrent/metastatic squamous cell carcinomas

      Forster, M.; Metcalf, Robert; Sacco, J.; Kong, A.; Wheeler, G.; Forsyth, S.; Bhat, R.; Blair, K.; Ward, J; Lowe, H.; et al. (2020)
      Background: Patients with R/M SCC have low response rates to second line therapies, including PD-1 inhibitors nivolumab and pembrolizumab, representing an area of unmet clinical need. Cetuximab has modest activity as a single agent but potentiates the activity of radiotherapy in locally advanced head & neck SCC (HNSCC) and chemotherapy in R/M HNSCC. Cetuximab initiates Natural Killer cell antibodydependent cell-mediated cytotoxicity, resulting in an anti-tumour immune response and the potential to augment the activity of PD-1/PD-L1 inhibition.Methods: Trial entry required histologically confirmed R/M SCC of any site, unselected by PD-L1 expression, considered incurable by local therapies and no previous treatment with cetuximab for recurrent/metastatic disease. Prior therapy with anti- PD-1, anti-PD-L1 or anti-PD-L2 was excluded. Patients had avelumab 10 mg/kg + cetuximab 500 mg/m2 intravenously every 2 weeks, for up to 1 year. Primary endpoint was occurrence of dose-limiting toxicity within 42 days of treatment starting, graded using CTCAE v5. Secondary endpoints were objective response (ORR) and disease control rate (DCR) at 6 and 12 months using iRECIST. Results: 16 patients, median age 58 years (range 34 e 88), were enrolled from 2 UK hospitals between July 2018 and October 2019. The trial stopped after completing the safety run-in. 5 patients remain on treatment, 9 stopped treatment early (7 disease progression, 1 patient choice, 1 due to risk of COVID-19). 2 patients died whilst on treatment (both unrelated to trial treatment). Grade 3 AEs were seen in 4 patients and grade 5 in 1 patient. None were related to trial treatment. No patients experienced dose-limiting toxicity. Of 10 patients evaluable for response by iRECIST 2 (20%) had complete response, 3 (30%) had partial response and 4 (40%) had stable disease as their best response, representing an ORR of 50%. One patient had confirmed disease progression. In 6 patients who remained on trial for >6 months, all 6 had disease control at 6 months (2 CR, 1 PR, 3 SD). Conclusions: Avelumab + cetuximab is safe and tolerable, and demonstrates promising efficacy in R/M SCC patients.
    • Earliest radiological progression in glioblastoma by multidisciplinary consensus review.

      Eijgelaar, R; Bruynzeel, A; Lagerwaard, F; Müller, D; Teunissen, F; Barkhof, F; van Herk, Marcel; De Witt Hamer, P; Witte, M; Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands (2018-05-18)
      Detection of glioblastoma progression is important for clinical decision-making on cessation or initiation of therapy, for enrollment in clinical trials, and for response measurement in time and location. The RANO-criteria are considered standard for the timing of progression. To evaluate local treatment, we aim to find the most accurate progression location. We determined the differences in progression free survival (PFS) and in tumor volumes at progression (Vprog) by three definitions of progression.
    • Early adaptation of colorectal cancer cells to the peritoneal cavity is associated with activation of 'stemness' programs and local inflammation

      Barriuso, Jorge; Nagaraju, R. T.; Belgamwar, Shreya; Chakrabarty, Bipasha; Burghel, G. J.; Schlecht, H.; Foster, Lucy; Kilgour, Elaine; Wallace, A. J.; Braun, Michael S; et al. (2020)
      Purpose: At diagnosis, colorectal cancer presents with synchronous peritoneal metastasis in up to 10% of patients. The peritoneum is poorly characterized with respect to its super-specialised microenvironment. Our aim was to describe the differences between peritoneal metastases and their matched primary tumours excised simultaneously at the time of surgery. Also, we tested the hypothesis of these differences being present in primary colorectal tumours and having prognostic capacity. Experimental design: We report a comprehensive analysis of thirty samples from peritoneal metastasis with their matched colorectal cancer primaries obtained during cytoreductive surgery. We tested and validated the prognostic value of our findings in a pooled series of 660 colorectal cancer primary samples with overall survival (OS) information and 743 samples with disease free survival (DFS) information from publicly available databases. Results: We identified 20 genes dysregulated in peritoneal metastasis that promote an early increasing role of 'stemness' in conjunction with tumour favourable inflammatory changes. When adjusted for age, gender and stage, the 20-gene peritoneal signature proved to have prognostic value for both OS (adjusted-hazard ratio (HR) for the high-risk group (vs low-risk) 2.32 (95% confidence interval (CI) 1.69-3.19; p-value < 0.0001)) and for DFS (adjusted-HR 2.08 (95%CI 1.50-2.91; p-value < 0.0001)). Conclusions: Our findings indicated that the activation of "stemness" pathways and adaptation to the peritoneal specific environment are key to early stages of peritoneal carcinomatosis. The in-silico analysis suggested that this 20-gene peritoneal signature may hold prognostic information with potential for development of new precision medicine strategies in this setting.
    • Early cellular events in colorectal carcinogenesis.

      Renehan, Andrew G; O'Dwyer, Sarah T; Haboubi, Najib; Potten, Christopher S; Department of Surgery, Christie Hospital NHS Trust, Manchester, UK, Department of Histopathology, Trafford General Hospital, Manchester, UK, Epistem Ltd, Manchester, UK. (2002-03)
      Colorectal cancer develops through a multistage process recognizable at a histopathological level by progression from normal mucosa to invasive carcinoma (the adenoma-carcinoma sequence). For many years, it has been hypothesized that increased cell proliferation in the colonic crypt represents the earliest recognizable stage in this sequence. This perspective is now changing. While several human studies have reported increased crypt cell proliferation in samples from at-risk patients, there are many inconsistencies and paradoxes in their conclusions. In addition, it is appreciated that the process of apoptosis (programmed cell death) is vital for normal crypt homeostasis and its impairment may be an early event in the neoplastic process. It is now believed that aberrant crypt foci (ACFs) represent the earliest step in colorectal carcinogenesis. Two ACF types are identifiable: hypercellular and dysplastic. Increased proliferative activity may be seen in both, but the dysplastic entity is most relevant to carcinogenesis. Animal and human studies support the notion that ACFs grow by crypt fission leading to the formation of microadenomas. Adenomas are monoclonal expansions of an altered cell, but very early lesions may be polyclonal. There are outward and inward theories of polypoid growth, and evidence to support both mechanisms. The ACF assay has become a useful tool to detect carcinogens in animal studies but has been less frequently used in human studies. For future cancer chemopreventive and risk assessment studies in humans, the identification and quantification of ACFs should be considered a more effective intermediate marker of risk than the determination of crypt cell proliferation alone.
    • Early central nervous system involvement in adults with acute non-myelogenous leukaemia.

      Lister, T; Whitehouse, J; Beard, M; Paxton, A; Brearley, R; Brown, L; Wrigley, P; Crowther, Derek (1977-04)
      Of 47 consecutive patients aged 15-60 years with acute non-myelogenous leukaemia (ANML) (40 acute lymphoblastic leukaemia (ALL); 5 acute Burkitt-like leukaemia (ABLL), 2 acute undifferentiated leukaemia (AUL) treated with a standard chemotherapy protocol (OPAL), 31 achieved complete remission (28/40(70%) of patients with ALL). CNS leukaemia occurred in 4/16 non-remitters, and in 6 patients who achieved complete remission (CR). CNS leukaemia occurred in all 5 patients with acute Burkitt-like leukaemia. 4/28 patients with ALL achieving CR had evidence of CSF involvement on cytocentrifuge examination shortly after CR. The apparent risk of early CNS disease suggests that prophylactic CNS therapy should be given early in the treatment of acute non-myelogenous leukaemia.
    • Early change in glucose metabolic rate measured using FDG-PET in patients with high-grade glioma predicts response to temozolomide but not temozolomide plus radiotherapy.

      Charnley, Natalie; West, Catharine M L; Barnett, C; Brock, Cathryn S; Bydder, Graeme M; Glaser, Mark; Newlands, Edward S; Swindell, Ric; Matthews, Julian C; Price, Patricia M; et al. (2006-10-01)
      PURPOSE: To compare the ability of positron emission tomography (PET) to predict response to temozolomide vs. temozolomide plus radiotherapy. METHODS AND MATERIALS: Nineteen patients with high-grade glioma (HGG) were studied. Patients with recurrent glioma received temozolomide 75 mg/m2 daily for 7 weeks (n=8). Newly diagnosed patients received temozolomide 75 mg/m2 daily plus radiotherapy 60 Gy/30 fractions over 6 weeks, followed by six cycles of adjuvant temozolomide 200 mg/m2/day (Days 1-5 q28) starting 1 month after radiotherapy (n=11). [18F]Fluorodeoxyglucose ([18F]FDG) PET scan and magnetic resonance imaging (MRI) were performed at baseline, and 7 and 19 weeks after initiation of temozolomide administration. Changes in glucose metabolic rate (MRGlu) and MRI response were correlated with patient survival. RESULTS: In the temozolomide-alone group, patients who survived>26 vs. or=25%, survived longer than nonresponders with mean survival times of 75 weeks (95% CI, 34-115 vs. 20 weeks (95% CI, 14-26) (p=0.0067). In the small group of patients studied, there was no relationship between MRI response and survival (p=0.52). For patients receiving temozolomide plus radiotherapy, there was no difference in survival between PET responders and nonresponders (p=0.32). CONCLUSIONS: Early changes in MRGlu predict response to temozolomide, but not temozolomide plus radiotherapy.
    • Early changes in the haemostatic and procoagulant systems after chemotherapy for breast cancer.

      Kirwan, C C; McDowell, G; McCollum, C N; Kumar, Shant; Byrne, Ged J; Department of Surgery, South Manchester University Hospitals Trust, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LT, UK. (2008-10-07)
      Venous thromboembolism (VTE) following breast cancer chemotherapy is common. Chemotherapy-induced alterations in markers of haemostasis occur during chemotherapy. It is unclear how rapidly this occurs, whether this is upregulated in patients developing VTE and whether changes predict for VTE. Markers of haemostasis, functional clotting assays and vascular endothelial growth factor were measured before chemotherapy and at 24 h, 4 days, 8 days and 3 months following commencement of chemotherapy in early and advanced breast cancer patients and in age- and sex-matched controls. Duplex ultrasound imaging was performed after 1 month or if symptomatic. Of 123 patients, 9.8% developed VTE within 3 months. Activated partial thromboplastin time (APTT), prothrombin time (PT), D-dimer, fibrinogen, platelet count, VEGF and fibrinogen were increased in cancer. Fibrinogen, D-dimer, VEGF and tissue factor were increased, at baseline, in patients subsequently developing VTE. D-dimer of less than 500 ng ml(-1) has a negative predictive value of 97%. Activated partial thromboplastin time, PT and thrombin-antithrombin showed significantly different trends, as early as within 24 h, in response to chemotherapy in patients subsequently developing VTE. Markers of coagulation and procoagulants are increased, before chemotherapy, in patients who subsequently develop VTE. A group of patients at minimal risk of VTE can be identified, allowing targeted thrombopropylaxis to the higher risk group.
    • Early clinical evaluation of a novel three-dimensional structure delineation software tool (SCULPTER) for radiotherapy treatment planning.

      McBain, Catherine A; Moore, Christopher J; Green, Matthew M L; Price, Gareth J; Sykes, Jonathan R; Amer, Aminah; Khoo, Vincent S; Price, Patricia M; Academic Department of Radiation Oncology, The University of Manchester, Manchester, UK. (2008-08)
      Modern radiotherapy treatment planning (RTP) necessitates increased delineation of target volumes and organs at risk. Conventional manual delineation is a laborious, time-consuming and subjective process. It is prone to inconsistency and variability, but has the potential to be improved using automated segmentation algorithms. We carried out a pilot clinical evaluation of SCULPTER (Structure Creation Using Limited Point Topology Evidence in Radiotherapy) - a novel prototype software tool designed to improve structure delineation for RTP. Anonymized MR and CT image datasets from patients who underwent radiotherapy for bladder or prostate cancer were studied. An experienced radiation oncologist used manual and SCULPTER-assisted methods to create clinically acceptable organ delineations. SCULPTER was also tested by four other RTP professionals. Resulting contours were compared by qualitative inspection and quantitatively by using the volumes of the structures delineated and the time taken for completion. The SCULPTER tool was easy to apply to both MR and CT images and diverse anatomical sites. SCULPTER delineations closely reproduced manual contours with no significant volume differences detected, but SCULPTER delineations were significantly quicker (p<0.05) in most cases. In conclusion, clinical application of SCULPTER resulted in rapid and simple organ delineations with equivalent accuracy to manual methods, demonstrating proof-of-principle of the SCULPTER system and supporting its potential utility in RTP.
    • Early clinical experience with cabozantinib for advanced renal cell carcinoma in the UK: real-world treatment pathways and clinical outcomes

      Venugopal, B.; Pillai, Manon; Powles, T.; Savage, P.; Michael, A.; Fife, K.; Klair, B.; Perrot, V.; Szabados, B.; Beatson West of Scotland Cancer Centre, NHS Greater Glasgow and Clyde, UK (2021)
      Background: Cabozantinib monotherapy is approved in the UK for patients with treatment-naïve intermediate- or poor-risk advanced renal cell carcinoma (aRCC), or patients who received prior vascular endothelial growth factor-targeted therapy. Data are limited on the real-world use of cabozantinib for aRCC. Patients and methods: CERES (NCT03696407) was a retrospective study of patients with aRCC who received cabozantinib through the UK managed access programme (MAP; August 2016-July 2017), at which time cabozantinib had European regulatory approval for second- or later-line use only. The study objectives were to characterize aRCC treatment patterns and evaluate cabozantinib effectiveness. Outcomes were stratified by cabozantinib treatment line, MAP treatment date (months 0-7 vs. 8-12) and (post hoc) Charlson Comorbidity Index (CCI; ≥ 6 vs. < 6). Results: Of 100 patients included, 99% had stage IV disease, 63% had a CCI ≥ 6 and 81% had an Eastern Cooperative Oncology Group Performance Status 0-1. Median (range) duration of follow-up was 10.8 (0.4-33.5) months. Cabozantinib was administered as second-line, third-line and fourth- or later-line in 41%, 31% and 28% of patients, respectively. Most patients (84%) initiated cabozantinib at 60 mg. Average (range) cabozantinib dose was 45.5 (19.6-59.8) mg/day; 66% of patients had ≥ 1 dose reduction. Disease progression was the most common reason for discontinuation (65.1%). Median (95% confidence interval) progression-free survival (PFS) and overall survival (OS) were 6.01 (5.16-7.85) and 10.84 (7.92-16.85) months, respectively. Overall response rate was 34.5%; disease control rate 70.1% and duration of response 6.9 (1.8-26.9) months. No significant differences in survival estimates were observed between treatment line or treatment date subgroups. Total CCI score ≤ 6 (vs. > 6) was associated with prolonged median PFS and OS. Conclusion: Cabozantinib demonstrated clinical activity in this UK real-world aRCC population. The results provide a benchmark for future real-world studies in aRCC.
    • Early demise from high grade serous ovarian cancer is predictable and likely related to tumour biology

      Hawarden, A; Russell, B; Gee, M; Skayali, F; Edmondson, M; Clamp, Andrew R; Jayson, Gordon C; Crosbie, E; Edmondson, R; Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary’s Hospital,Manchester, UK (2019)
    • Early detection of HPV-associated oropharyngeal cancer - Authors' reply

      Graham, Donna; Prue, G; Baker, P; Nutting, C; Greenhouse, P; Lawler, M; Christie NHS Foundation Trust, Manchester, UK (2019)
    • Early detection of residual breast cancer through a robust, scalable and personalized analysis of circulating tumour DNA (ctDNA) antedates overt metastatic recurrence

      Coombes, RC; Armstrong, Anne C; Ahmed, S; Page, K; Hastings, RK; Salari, R; Sethi, H; Boydell, AR; Shchegrova, SV; Fernandez-Garcia, D; et al. (2019)
      Background: Many breast cancer patients relapse after primary treatment but there are no reliable tests to detect distant metastases before they become overt. Here we show earlier identification of recurring patients through a scalable personalised ctDNA analysis. The method is applicable to all patients, and not limited to hot-spot mutations typically detected by gene panels. Methods: Forty-nine non-metastatic breast cancer patients were recruited following surgery and adjuvant therapy. Plasma samples (n=208) were serially collected semi-annually. Using the analytically validated SignateraTM workflow, we determined mutational signatures from primary tumour whole exome data and designed personalised assays targeting 16 variants with high sensitivity by ultra-deep sequencing (average >100,000X). The patient-specific assay was used to detect the presence of the mutational signature in the plasma. Results: In 16 of 18 (89%) clinically-relapsing patients, ctDNA was detected ahead of metastatic relapse being diagnosed by clinical examination, radiological and biochemical (CA15-3) measurements, and remained ctDNA-positive through follow-up. Of the 2 patients not detected by ctDNA, one had a small local recurrence only (now resected) and the other had three primary tumours. None of the 31 non-relapsing patients were ctDNA-positive at any time point (n=142). Metastatic relapse was predicted by Signatera with high accuracy and a lead time of up to 2 years (median=9.5 months). Conclusions: The use of a scalable patient-specific ctDNA-based validated workflow detects breast cancer recurrence ahead of clinical detection. Accurate and earlier prediction by ctDNA analysis could provide a means of monitoring breast cancer patients in need of second-line salvage adjuvant therapy in order to prevent overt life-threatening metastatic progression.
    • Early diagnosis of acromegaly: computers vs clinicians.

      Miller, Ralph; Learned-Miller, Erik G; Trainer, Peter J; Paisley, Angela N; Blanz, Volker; Division of Endocrinology, Department of Medicine, University of Kentucky, Lexington, KY (2011-08)
      Background  Early diagnosis of a number of endocrine diseases is theoretically possible by the examination of facial photographs. One of these is acromegaly. If acromegaly were found, early in the course of the disease, morbidity would be lessened and cures more likely. Objectives, design, patients, measurements  Our objective was to develop a computer program which would separate 24 facial photographs, of patients with acromegaly, from those of 25 normal subjects. The key to doing this was to use a previously developed database that consisted of three-dimensional representations of 200 normal person's heads (SIGGRAPH '99 Conference Proceedings, 1999). We transformed our 49, two-dimensional photos into three-dimensional constructs and then, using the computer program, attempted to separate them into those with and without the features of acromegaly. We compared the accuracy of the computer to that of 10 generalist physicians. A second objective was to examine, by a subjective analysis, the features of acromegaly in the normal subjects of our photographic database. Results  The accuracy of the computer model was 86%; the average of the 10 physicians was 26%. The worst individual physician, 16%, the best, 90%. The faces of 200 normal subjects, the original faces in the database, could be divided into four groups, averaged by computer, from those with fewer to those with more features of acromegaly. Conclusions  The present computer model can sort photographs of patients with acromegaly from photographs of normal subjects and is much more accurate than the sorting by practicing generalists. Even normal subjects have some of the features of acromegaly. Screening with this approach can be improved with automation of the procedure, software development and the identification of target populations in which the prevalence of acromegaly may be increased over that in the general population.
    • Early experience with MR-guided adaptive radiotherapy using a 1.5 T MR-Linac: First 6 months of operation using adapt to shape workflow

      de Leon, J.; Crawford, D.; Moutrie, Z.; Alvares, S.; Hogan, L.; Pagulayan, C.; Jelen, U.; Loo, C.; Aylward, Jack D; Condon, K.; et al. (2021)
      Introduction: The magnetic resonance linear accelerator (MRL) offers improved soft tissue visualization to guide daily adaptive radiotherapy treatment. This manuscript aims to report initial experience using a 1.5 T MRL in the first 6 months of operation, including training, workflows, timings and dosimetric accuracy. Methods: All staff received training in MRI safety and MRL workflows. Initial sites chosen for treatment were stereotactic and hypofractionated prostate, thoraco-abdomino-pelvic metastasis, prostate bed and bladder. The Adapt To Shape (ATS) workflow was chosen to be the focus of treatment as it is the most robust solution for daily adaptive radiotherapy. A workflow was created addressing patient suitability, simulation, planning, treatment and peer review. Treatment times were recorded breaking down into the various stages of treatment. Results: A total of 37 patients were treated and 317 fractions delivered (of which 313 were delivered using an ATS workflow) in our initial 6 months. Average treatment times over the entire period were 50 and 38 min for stereotactic and non-stereotactic treatments respectively. Average treatment times reduced each month. The average difference between reference planned and ionization chamber measured dose was 0.0 � 1.4%. Conclusion: The MRL was successfully established in an Australian setting. A focus on training and creating a detailed workflow from patient selection, review and treatment are paramount to establishing new treatment programmes.
    • Early hormonal data from a multicentre phase II trial using transdermal oestrogen patches as first-line hormonal therapy in patients with locally advanced or metastatic prostate cancer.

      Langley, Ruth E; Godsland, Ian F; Kynaston, Howard; Clarke, Noel W; Rosen, Stuart D; Morgan, Rachel C; Pollock, Philip; Kockelbergh, Roger; Lalani, El-Nasir; Dearnaley, David P; et al. (2008-08)
      OBJECTIVE: To assess the hormonal effects of Fem7 (Merck, KGaA, Darmstadt, Germany) 100 microg transdermal oestrogen patches on men undergoing first-line androgen-deprivation therapy for prostate cancer. PATIENTS AND METHODS: PATCH is a multicentre, randomized, phase II trial for men with locally advanced or metastatic prostate cancer, comparing luteinizing hormone-releasing hormone agonist therapy with oestrogen patches. To assess the dosing schedule for the patches, as this was the first time that this brand of patch had been used in men, and to reassure patients and participating clinicians, the Independent Data Monitoring Committee agreed to early release of hormonal data from this study. RESULTS: Oestradiol, testosterone and prostate-specific antigen (PSA) levels are presented for the first group of 14 patients who received the patches (with 1 withdrawal) and for whom there were > or =12 weeks of follow-up by March 2007. After 12 weeks, testosterone levels (nmol/L) in eight of the 13 patients were <1.7, two were 1.7-2 and three were >2. The median (range) serum oestradiol levels was 442 (52.1-1542) pmol/L and all patients had a PSA response, with eight having a PSA level of <4 ng/mL. CONCLUSION: These results confirm that oestrogen patches produce castrate levels of testosterone and concomitant PSA responses. They also highlighted the potential differences between different brands of oestrogen patches, and the need to monitor hormonal response, toxicity and efficacy until more experience with oestrogen patches for this clinical indication is obtained. The number of patches recommended in the PATCH study has now been increased.
    • Early infliximab in life-threatening immune-mediated pneumonitis

      Cooksley, Timothy J; Marshall, W; Gupta, A; The Christie, Wilmslow Road, Manchester, M20 4BX (2019)
    • Early investigation and initiation of therapy for invasive pulmonary aspergillosis in leukaemic and bone marrow transplant patients.

      Barnes, Amanda J; Oppenheim, B A; Chang, James; Morgenstern, Godfrey R; Scarffe, J Howard; Public Health Laboratory, Withington Hospital, Manchester, UK. (1999)
      Invasive fungal infections are an increasingly common problem in cancer patients and in other vulnerable groups. Invasive pulmonary aspergillosis (IPA) in the neutropenic host presents particular challenges in terms of diagnosis and therapy. Against the background of a recognized problem of invasive aspergillosis in haematology/oncology patients treated at the Christie Hospital, we undertook a prospective study in patients at risk for IPA. The aim of the study was to improve outcome by using the linked strategies of first, early diagnosis, and secondly, early aggressive therapy with a lipid-associated formulation of amphotericin B, amphotericin B colloidal dispersion ('Amphocil'). Early investigation comprised the use of high-resolution computerized tomography scanning of the thorax and fibreoptic bronchoscopy to obtain bronchoalveolar lavage specimens, processed using conventional detection and culture methods. Using this approach, the incidence of proven or probable IPA in patients with acute leukaemia was 9%. Prompt initiation of amphotericin B colloidal dispersion therapy led to a successful outcome in 11 of 13 patients, compared with a mortality of 100% in historical controls.