P N Plowman

St. Michael's Hospital, Toronto, Ontario, Canada

Are you P N Plowman?

Claim your profile

Publications (204)838.98 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Accurate and rapid methods for the detection of DNA damage foci in eukaryotic cells are central to DNA repair studies, which identify differences in DNA repair capacity in cell lines. Such assays have been important in delineating mechanisms of DNA repair in human cells. Previously we were the first to demonstrate the use of imaging flow cytometry for the detection of γ-H2AX foci in cells exposed to ionizing radiation causing the induction of DNA strand breaks. In this report we extend these studies and show an enhancement of foci quantitation and image resolution using next generation imaging flow cytometry with the Amnis Imagestream(X) Mark II. We demonstrate using cell lines derived from normal individuals, and DNA double strand break repair defective cells that the number of foci observed is significantly increased when using 60× as compared to 40× magnification. Also, foci numbers and resolution is further increased with the application of the focus stacking (Extended Depth of Field-EDF) capacity activated. This report represents the first such demonstration of multimagnification and EDF for the enhanced quantitation of DNA damage in cells and provides a level of resolution, which near matches in situ microscopy methods for the detection of γ-H2AX foci. © 2015 International Society for Advancement of Cytometry. © 2015 International Society for Advancement of Cytometry.
    Cytometry Part A 06/2015; DOI:10.1002/cyto.a.22697 · 3.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Low-grade ocular adnexal lymphoma is a rare disease and often treated with local radiotherapy to varying doses. Most previously reported studies have a very heterogeneous patient population and treatments. We report the outcomes from a 10 year cohort of patients at our institution treated with primary radiation therapy.Materials and methodsWe analysed a retrospective case series of patients with stage IE low-grade ocular adnexal lymphoma including a review of case notes, histological reports and radiotherapy charts. We assessed local and distant tumour control and relapse rates in addition to toxicity. Disease-free survival was estimated using the Kaplan–Meier method.ResultsIn total, 81 patients and 85 orbits were treated with primary radiotherapy to a median dose of 30 Gy in 15 fractions over 3 weeks. Seventy-nine per cent were treated with standard MV external beam radiotherapy to the whole orbit and 21% with a lens-sparing technique. The median follow-up was 4.4 years (range 0.2–10.4). Local control rates were 100%, with 5% of patients experiencing disease relapse elsewhere. No patients died from lymphoma. Cumulative acute toxicity rates were 51% (mainly erythema and conjunctivitis) and late toxicity rates were 8% (mainly cataract). The lens-sparing technique was associated with a significant reduction in cataract rate (P = 0.013) and an increase in acute toxicity (P < 0.001).Conclusions This study has shown excellent local control rates and acceptable toxicity from the treatment of stage IE low-grade ocular adnexal lymphoma with localised radiotherapy to a median dose of 30 Gy in 15 fractions over 3 weeks.
    Clinical Oncology 10/2014; 27(3). DOI:10.1016/j.clon.2014.10.002 · 2.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background:(131)I-meta-iodobenzylguanidine ((131)I-MIBG) has been in therapeutic use since 1980s. Newer treatment modalities are emerging for neuroendocrine tumours (NETs) and chromaffin cell tumours (CCTs), but many of these do not yet have adequate long-term follow-up to determine their longer term efficacy and sequelae.Methods:Fifty-eight patients with metastatic NETs and CCTs who had received (131)I-MIBG therapy between 2000 and 2011 were analysed. Survival and any long-term haematological or renal sequelae were investigated.Results:In the NET group, the overall median survival and median survival following the diagnosis of metastatic disease was 124 months. The median survival following the commencement of (131)I-MIBG was 66 months. For the CCT group, median survival had not been reached. The 5-year survival from diagnosis and following the diagnosis of metastatic disease was 67% and 67.5% for NETs and CCTs, respectively. The 5-year survival following the commencement of (131)I-MIBG therapy was 68%. Thirty-two patients had long-term haematological sequelae: 5 of these 32 patients developed haematological malignancies. Two patients developed a mild deterioration in renal function.Conclusion:Long follow up of (131)I-MIBG therapy reveals a noteable rate of bone marrow toxicities and malignancy and long term review of all patients receiving radionuclide therapies is recommended.British Journal of Cancer advance online publication, 16 July 2013; doi:10.1038/bjc.2013.365 www.bjcancer.com.
    British Journal of Cancer 07/2013; 109(3). DOI:10.1038/bjc.2013.365 · 4.82 Impact Factor
  • Journal of Cancer Therapy 01/2013; 04(11):44-52. DOI:10.4236/jct.2013.411A006
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background:The objective of this study was to determine the molecular mechanisms responsible for cellular radiosensitivity in two human fibroblast cell lines 84BR and 175BR derived from two cancer patients.Methods:Clonogenic assays were performed following exposure to increasing doses of gamma radiation to confirm radiosensitivity. γ-H2AX foci assays were used to determine the efficiency of DNA double-strand break (DSB) repair in cells. Quantitative PCR (Q-PCR) established the expression levels of key DNA DSB repair genes. Imaging flow cytometry using annexin V-FITC was used to compare artemis expression and apoptosis in cells.Results:Clonogenic cellular hypersensitivity in the 84BR and 175BR cell lines was associated with a defect in DNA DSB repair measured by the γ-H2AX foci assay. The Q-PCR analysis and imaging flow cytometry revealed a two-fold overexpression of the artemis DNA repair gene, which was associated with an increased level of apoptosis in the cells before and after radiation exposure. Overexpression of normal artemis protein in a normal immortalised fibroblast cell line NB1-Tert resulted in increased radiosensitivity and apoptosis.Conclusion:We conclude that elevated expression of artemis is associated with higher levels of DNA DSB, radiosensitivity and elevated apoptosis in two radio-hypersensitive cell lines. These data reveal a potentially novel mechanism responsible for radiosensitivity and show that increased artemis expression in cells can result in either radiation resistance or enhanced sensitivity.
    British Journal of Cancer 10/2012; 107(9):1506-13. DOI:10.1038/bjc.2012.443 · 4.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Phase III trials in the 1990s for squamous cell carcinoma of the anus (SCCA) demonstrated 5-fluorouracil (5FU) and mitomycinC (MMC) chemoradiation (CRT) improved outcome compared to radiation (RT) alone, but local recurrence remained significant. This prospective pilot study intensified treatment by integrating 3 cytotoxic drugs into CRT and maintenance chemotherapy. CRT comprised 5-FU 1000 mg/m(2) days 1-4,29-32, MMC 10 mg/m(2) day 1 and Cisplatin (CDDP) 60 mg/m(2) days1 and 29, with 45 Gy in 25 daily fractions, followed by a 15 Gy boost. Maintenance chemotherapy started 4-8 weeks later, three courses repeated every 21 days, using 5-FU/CDDP doses above, with MMC reduced to 7 mg/m(2) and administered with the first and third cycles. In CRT only 14/19 (74%) patients received protocol-defined chemotherapy doses in week 5. Compliance to maintenance chemotherapy was poor. 15/19 started cycle 1, 13 started cycle 2 and 11 cycle 3. 17/19 experienced G3-G5 toxicity (16 Grade 3/4 and one Grade 5). 16/19 patients (84%) remain alive and disease-free - median follow-up 79 months (34-115). Despite favourable results, the significant toxicity and low compliance of the three-drug CRT regimen used, deemed it unsuitable for testing in a phase III trial. A two-drug maintenance regimen was explored in the ACT II trial.
    Radiotherapy and Oncology 07/2012; 104(2):155-60. DOI:10.1016/j.radonc.2012.06.006 · 4.86 Impact Factor
  • D K Woolf, M Ahmed, P N Plowman
    [Show abstract] [Hide abstract]
    ABSTRACT: Lymphomas of the orbit and eye are rare conditions that should be treated as separate entities due to the differences in presumed aetiology, investigations, management and outcomes. Orbital lymphoma is most often of low-grade histology; thyroid eye disease may predispose and chlamydial infection has been suggested as a trigger. Commonly, stage IE, in most cases, can be managed with radiotherapy alone using either a kilovoltage portal for conjunctival disease or a wedged pair of megavoltage beams for more infiltrative disease to a dose of 30 Gy in 15 fractions over 3 weeks. However, medical therapy is being investigated, including a rituximab-only approach for conjunctival-only presentations. The cure rate for stage IE disease is very high. In contrast, primary ocular lymphoma is often of high-grade histology, in particular diffuse large B-cell lymphoma, and can be regarded as one end of primary central nervous system lymphoma - both eyes and brain being at risk. Immunosuppression predisposes to the disease. Management consists of an initial high-dose chemotherapy regimen with methotrexate. In most cases, this should be followed by radiotherapy to the whole brain and globes to a dose of 30-36 Gy with a boost to bulk/presenting disease. Cure rates are rarely above 50%.
    Clinical Oncology 04/2012; 24(5):339-44. DOI:10.1016/j.clon.2012.03.001 · 2.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The measurement of γ-H2AX foci induction in cells provides a sensitive and reliable method for the quantitation of DNA damage responses in a variety of cell types. Accurate and rapid methods to conduct such observations are desirable. In this study, we have employed the novel technique of multispectral imaging flow cytometry to compare the induction and repair of γ-H2AX foci in three human cell types with different capacities for the repair of DNA double strand breaks (DSB). A repair normal fibroblast cell line MRC5-SV1, a DSB repair defective ataxia telangiectasia (AT5BIVA) cell line, and a DNA-PKcs deficient cell line XP14BRneo17 were exposed to 2 Gy gamma radiation from a (60)Cobalt source. Thirty minutes following exposure, we observed a dramatic induction of foci in the nuclei of these cells. After 24 hrs, there was a predictable reduction on the number of foci in the MRC5-SV1 cells, consistent with the repair of DNA DSB. In the AT5BIVA cells, persistence of the foci over a 24-hr period was due to the failure in the repair of DNA DSB. However, in the DNA-PKcs defective cells (XP14BRneo17), we observed an intermediate retention of foci in the nuclei indicative of partial repair of DNA DSB. In summary, the application of imaging flow cytometry has permitted an evaluation of foci in a large number of cells (20,000) for each cell line at each time point. This provides a novel method to determine differences in repair kinetics between different cell types. We propose that imaging flow cytometry provides an alternative platform for accurate automated high through-put analysis of foci induction in a variety of cell types.
    Cytometry Part A 02/2012; 81(2):130-7. DOI:10.1002/cyto.a.21171 · 3.07 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The normal tissue tolerance levels to fractionated radiotherapy have been appreciated by a century of careful clinical observations and radiobiological studies in animals. During clinical fractionated radiotherapy, these normal tissue tolerance levels are respected, and severe sequelae of radiotherapy are avoided in the majority of patients. Notwithstanding, a minority of patients experience unexpectedly severe normal tissue reactions. The ability to predict which patients might form this minority would be important. We have conducted a study to develop a rapid and reliable diagnostic test to predict excessive normal tissue toxicity (NTT) in radiotherapy patients. A flow cytometric immunocytochemical assay was used to measure DNA damage in peripheral blood lymphocytes (PBL) from cancer patients exposed to 2-Gy gamma radiation. DNA damage and repair was measured by induction of cellular γ-H2AX in unirradiated and exposed cells at specific time points following exposure. In 12 cancer patients that experienced severe atypical NTT following radiotherapy, there was a failure to repair DNA double-strand breaks (DSB) as measured by γ-H2AX induction and persistence. In ten cancer patients that experienced little or no NTT and in seven normal (noncancer controls), efficient repair of DNA DSB was observed in the γ-H2AX assay. We conclude that a flow cytometric assay based on γ-H2AX induction in PBL of radiotherapy patients may represent a robust, rapid and reliable biomarker to predict NTT during radiotherapy. Further research is required with a larger patient cohort to validate this important study.
    International Journal of Cancer 12/2011; 129(12):2928-34. DOI:10.1002/ijc.25953 · 5.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Intensity-modulated radiotherapy (IMRT) is a relatively new technique of delivering external beam radiotherapy that is becoming increasingly available in the UK. This paper summarises the introduction and initial clinical work in IMRT over the period 2004-2009. Physics aspects of commissioning are described, including the development of a robust method of quality control using a sweeping gap test. Details of the organisational changes necessary to introduce IMRT are given. The clinical selection and practice in head and neck sites are described, together with promising early results on the maintenance of salivary flow after IMRT. A summary of research into optimal planning for pelvic cancer follows. The controversial areas of breast and paediatric IMRT are discussed with recommendations on practice. The potential for concomitant boost therapy is exemplified in the treatment of brain metastatic disease.
    Clinical Oncology 10/2010; 22(8):666-74. DOI:10.1016/j.clon.2010.06.018 · 2.83 Impact Factor
  • European Journal of Endocrinology 08/2010; 163(2):357-8. DOI:10.1530/EJE-10-0498 · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cushing's disease (CD) in prepubertal children is very rare and presents important diagnostic and therapeutic challenges. We report experience of the management of this subpopulation of CD patients. Retrospective patient case note review. Between 1985 and 2008, 17 prepubertal children (13M, 4F), aged 5.7-14.1 years presented to our centre for diagnosis and management of CD. All children had subnormal linear growth and excessive weight gain at presentation. A high proportion (85% of males, 75% of females) had evidence of excessive virilisation. Striae and hypertension were seen in 41% of patients. The investigation with highest sensitivity (100%) for CD was excessive increase of serum cortisol to i.v. CRH (mean increase 113%). Pituitary imaging performed in all the patients showed poor concordance with findings at surgery (31%). In contrast bilateral simultaneous inferior petrosal sinus sampling (BSIPSS), performed in 11/16 subjects showed a high correlation with surgical findings (91%). In 16 patients, transsphenoidal selective adenomectomy (TSS) achieved a cure rate of 44%. However, in the 11 patients who had pre-operative BSIPSS, the cure rate was 64%. Of the 16 patients, 9 patients who were not cured by TSS received external pituitary radiotherapy. Prepubertal CD had distinctive features with increased frequency in males, abnormal auxology and excessive virilisation. The cortisol response to i.v. CRH administration was particularly exuberant and contributed to diagnosis. BSIPSS was much more helpful than pituitary imaging in localisation of the microadenoma and was associated with improved cure rate by TSS.
    European Journal of Endocrinology 12/2009; 162(3):603-9. DOI:10.1530/EJE-09-0509 · 3.69 Impact Factor
  • Source
    A A Edwards, E Keggin, P N Plowman
    [Show abstract] [Hide abstract]
    ABSTRACT: Whole brain radiotherapy (WBRT) is the standard non-surgical treatment for brain metastatic disease, but rarely eradicates bulky metastases from most common cancers. Recent literature has demonstrated the safety and efficacy of delivering very high focal doses of radiation (by radiosurgical techniques) to the gross tumour volume of bulky brain metastases, thereby obtaining more certain local control than is achieved by WBRT. In this paper we report a study of 11 patients with bulky brain metastases in whom an intensity-modulated radiation therapy (IMRT) facility has been used to concomitantly boost the gross tumour volume of bulky brain metastatic disease (to 40 Gy) during a standard 30 Gy in 10 fractions WBRT schedule. No acute or subacute morbidity was encountered, and good early control data were noted. We discuss the perceived advantages of such a technique.
    The British journal of radiology 12/2009; 83(986):133-6. DOI:10.1259/bjr/28596848 · 1.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Radiotherapy-induced DNA double-strand breaks (DSBs) are critical cytotoxic lesions. Inherited defects in DNA DSB repair pathways lead to hypersensitivity to ionising radiation, immunodeficiency and increased cancer incidence. A patient with xeroderma pigmentosum complementation group C, with a scalp angiosarcoma, exhibited dramatic clinical radiosensitivity following radiotherapy, resulting in death. A fibroblast cell line from non-affected skin (XP14BRneo17) was hypersensitive to ionising radiation and defective in DNA DSB repair. To determine the genetic defect causing cellular radiation hypersensitivity in XP14BRneo17 cells. Functional genetic complementation whereby copies of human chromosomes containing genes involved in DNA DSB repair (chromosomes 2, 5, 8 10, 13 and 22) were individually transferred to XP14BRneo17 cells in an attempt to correct the radiation hypersensitivity. Clonogenic survival assays and gamma-H2AX immunofluorescence were conducted to measure radiation sensitivity and repair of DNA DSBs. DNA sequencing of defective DNA repair genes was performed. Transfer of chromosome 8 (location of DNA-PKcs gene) and transfection of a mammalian expression construct containing the DNA-PKcs cDNA restored normal ionising radiation sensitivity and repair of DNA DSBs in XP14BRneo17 cells. DNA sequencing of the DNA-PKcs coding region revealed a 249-bp deletion (between base pairs 3656 and 3904) encompassing exon 31 of the gene. We provide evidence of a novel splice variant of the DNA-PKcs gene associated with radiosensitivity in a patient with xeroderma pigmentosum and report the first double mutant in distinct DNA repair pathways being consistent with viability.
    Journal of Medical Genetics 10/2009; 47(3):176-81. DOI:10.1136/jmg.2009.068866 · 5.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We report the use of 'gamma knife' (GK) radiosurgery in 25 patients with pituitary adenomas not cured despite conventional therapy, including external beam radiotherapy. All patients had previously received conventional radiotherapy for a mean of 11.8 years prior to receiving GK; 23 out of 25 had also undergone pituitary surgery on at least one occasion. Seventeen had hyperfunctioning adenomas that still required medical therapy without an adequate biochemical control--ten somatotroph adenomas, six corticotroph adenomas and one prolactinoma, while eight patients had non-functioning pituitary adenomas (NFPAs). Following GK, mean GH fell by 49% at 1 year in patients with somatotroph tumours. Serum IGF1 fell by 32% at 1 year and by 38% at 2 years. To date, 80% of the patients with acromegaly have achieved normalisation of IGF1, and 30% have also achieved a mean GH level of <1.8 ng/ml correlating with normalised mortality. A total of 75% NFPAs showed disease stabilisation or shrinkage post GK. The patient with a prolactinoma showed a dramatic response: 75% reduction in prolactin at 2 years, with a marked shrinkage on magnetic resonance imaging. The results in corticotroph adenomas were variable. Prior to GK, 72% of the patients were panhypopituitary, and 42% of the remainder have developed new anterior pituitary hormone deficiencies to date. No other adverse events have been detected at a mean follow-up of 36.4 months. These data indicate that GK is a safe and effective adjunctive treatment for patients with NFPAs and acromegaly not satisfactorily controlled with surgery and radiotherapy.
    European Journal of Endocrinology 09/2009; 161(6):819-28. DOI:10.1530/EJE-09-0493 · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Radiation is implicated in the induction of second malignancies in children with bilateral retinoblastoma. There is a need to determine whether this risk can be justified by good visual outcome when external beam radiotherapy (EBRT) is used as a salvage treatment. To study the effectiveness of EBRT as a salvage treatment after failed primary chemotherapy and focal treatment in bilateral retinoblastoma. This is a retrospective observational case series. The outcome measures after EBRT are: rate of eye preservation, rate of tumour control, visual potential, visual acuity and radiation-induced side-effects. Thirty-six eyes (22 patients) were included. The median follow-up after EBRT was 40 months (19-165 months). Thirty-two eyes received lens-sparing radiotherapy, and four received whole-eye radiation. The rate of eye preservation was 83.3% (30/36 eyes). Twenty-four eyes (66.7%) were controlled by EBRT and required no further treatment. Of the 30 preserved eyes, 20 eyes (66.7%) had extramacular tumours without retinal detachment and therefore potential for central vision. The final visual acuity was recorded for 19 eyes. Ten eyes (52.6%) read 6/9-6/5, three eyes (15.8%) read 6/18-6/36, and six eyes (31.6%) read 6/60 or worse. Significant radiation- induced side effects were limited to cataracts and dry eyes with whole-eye radiation. There were no second cancers or deaths. Salvage EBRT is highly effective in preserving eyes with useful vision in bilateral retinoblastoma after failed chemotherapy and focal treatments. These results will help the parents and ophthalmologists of such patients to reach an informed decision when weighing up the benefits of EBRT against its potential oncogenic effect.
    The British journal of ophthalmology 04/2009; 93(7):891-4. DOI:10.1136/bjo.2007.129981 · 2.81 Impact Factor
  • H O'Donnell, K Cooke, N Walsh, P N Plowman
    [Show abstract] [Hide abstract]
    ABSTRACT: New technology - specifically intensity-modulated radiotherapy (IMRT) - is now being applied to breast radiotherapy and a recent dosimetric analysis confirmed the advantages of IMRT over 'wedge-only' plans. Such application to everyday practice raises new issues and here we present the early experience of IMRT-based breast irradiation in a single centre. We present cases of breast cancer treated by Tomotherapy-based IMRT, where the perceived advantages of IMRT are considerable. Cases presented are bilateral disease, left breast irradiation, pectus excavatum, prominent contralateral prosthesis and internal mammary chain disease. We discuss the practicalities of such treatment and the advantages over standard breast irradiation techniques. Advantages include better conformity of treatment with lowering of dosages to underlying organs at risk, for example ipsilateral lung and heart. There is improved coverage of the planning target volume, including regional nodes, without field junction problems. Planning, quality assurance and treatment delivery are more time consuming than for standard breast irradiation and the low dose 'bath' is increased. The standard radiotherapy tangential technique for breast/chest wall treatments has not significantly changed over many decades, whereas across many other tumour sites there have been great advances in radiotherapy technology. The dosimetric advantages of IMRT are readily apparent from our early experience. The wider spread of the lower dose zone (the low dose 'bath' of radiation) is a potential concern regarding late oncogenesis and methods to minimise such risks should be considered.
    Clinical Oncology 03/2009; 21(4):294-301. DOI:10.1016/j.clon.2009.01.010 · 2.83 Impact Factor
  • Source
    Clinical Endocrinology 12/2008; 55(5):575 - 587. DOI:10.1046/j.1365-2265.2001.01396.x · 3.35 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A 64-year-old woman was previously treated for Cushing's disease with trans-sphenoidal surgery, external beam radiotherapy and bilateral adrenalectomy. Progression of an aggressive corticotroph adenoma was evident 3 years post-adrenalectomy; involvement of the clivus was treated with surgery and gamma knife radiosurgery. Tumour spread through the skull base, occiput and left ear with persistent facial pain and left ear discharge; progression continued despite second gamma knife treatment. ACTH levels peaked at 2472 and 2265 pmol/l pre- and post-hydrocortisone respectively. Treatment with temozolomide resulted in a significant improvement in symptoms, a reduction of plasma ACTH to 389 pmol/l and regression of tumour on magnetic resonance imaging scan after four cycles of treatment. We propose that temozolomide is an effective and well-tolerated therapeutic tool for the treatment of Nelson's syndrome and a useful addition to the range of therapies available to treat this condition.
    European Journal of Endocrinology 12/2008; 160(1):115-9. DOI:10.1530/EJE-08-0557 · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To describe two patients with localized orbital amyloidosis and the response of their condition to surgical debulking followed by external beam radiotherapy. Retrospective noncomparative interventional case series. Stabilization or regression of orbital signs after treatment. Patients with biopsy-proven diagnosis of localized progressive orbital amyloidosis received 34 and 30 Gy fractionated external beam radiotherapy. The clinical case notes and histopathology for the two patients were reviewed. A 69-year-old man with orbital amyloid deposition in association with localized MALT lymphoma had a marked improvement in orbital signs following surgical debulking and radiotherapy, with no recurrence over two years. A 59-year-old woman with localized orbital amyloidosis showed regression of disease after surgical debulking and radiotherapy, with no evidence of recurrence after six years of follow-up. External beam radiotherapy following surgical debulking appears to halt the progression of localized orbital amyloidosis. Radiotherapy may be used in conjunction with surgical debulking of disease.
    Orbit (Amsterdam, Netherlands) 12/2008; 27(6):432-7. DOI:10.1080/01676830802350216

Publication Stats

3k Citations
838.98 Total Impact Points


  • 2008
    • St. Michael's Hospital
      Toronto, Ontario, Canada
  • 1992–2007
    • Great Ormond Street Hospital for Children NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2005
    • University of California, Davis
      • Department of Radiation Oncology
      Davis, CA, United States
  • 1986–2005
    • SickKids
      • Division of Hematology/Oncology
      Toronto, Ontario, Canada
  • 2004
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2003
    • Queen Mary, University of London
      Londinium, England, United Kingdom
  • 1990
    • Stanford Medicine
      Stanford, California, United States
    • University of Sussex
      • Centre for Genome Damage and Stability
      Brighton, England, United Kingdom
  • 1984–1986
    • Tulane University
      • Department of Medicine
      New Orleans, Louisiana, United States