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Murray L.,St Jamess Institute Of Oncology | Henry A.,St Jamess Institute Of Oncology | Hoskin P.,Mount Vernon Cancer Center | Siebert F.-A.,Klinik fur Strahlentherapie | Venselaar J.,Institute Verbeeten
Radiotherapy and Oncology | Year: 2014

The development of a radiation induced second primary cancer (SPC) is one the most serious long term consequences of successful cancer treatment. This review aims to evaluate SPC in prostate cancer (PCa) patients treated with radiotherapy, and assess whether radiation technique influences SPC. A systematic review of the literature was performed to identify studies examining SPC in irradiated PCa patients. This identified 19 registry publications, 21 institutional series and 7 other studies. There is marked heterogeneity in published studies. An increased risk of radiation-induced SPC has been identified in several studies, particularly those with longer durations of follow-up. The risk of radiation-induced SPC appears small, in the range of 1 in 220 to 1 in 290 over all durations of follow-up, and may increase to 1 in 70 for patients followed up for more than 10 years, based on studies which include patients treated with older radiation techniques (i.e. non-conformal, large field). To date there are insufficient clinical data to draw firm conclusions about the impact of more modern techniques such as IMRT and brachytherapy on SPC risk, although limited evidence is encouraging. In conclusion, despite heterogeneity between studies, an increased risk of SPC following radiation for PCa has been identified in several studies, and this risk appears to increase over time. This must be borne in mind when considering which patients to irradiate and which techniques to employ. © 2014 The Authors. Published by Elsevier Ireland Ltd.


Hill Q.A.,St Jamess Institute of Oncology | Rawstron A.C.,St Jamess Institute of Oncology | De Tute R.M.,St Jamess Institute of Oncology | Owen R.G.,St Jamess Institute of Oncology
Blood | Year: 2014

The purpose of this study was to use multiparameter flow cytometry to detect occult marrow disease (OMD) in patients with solitary plasmacytoma of bone and assess its value in predicting outcome. Aberrant phenotype plasma cells were demonstrable in 34 of 50 (68%) patients and comprised a median of 0.52% of bone marrow leukocytes. With a median follow-up of 3.7 years, 28 of 50 patients have progressed with a median time to progression (TTP) of 18 months. Progression was documented in 72% of patients with OMD vs 12.5% without (median TTP, 26 months vs not reached; P = .003). Monoclonal urinary light chains (ULC) were similarly predictive of outcome because progression was documented in 91% vs 44% without (median TTP, 16 vs 82 months; P < .001). By using both parameters, it was possible to define patients with an excellent outcome (lacking both OMD and ULC, 7.7% progression) and high-risk patients (OMD and/or ULC, 75% progression; P = .001). Trials of systemic therapy are warranted in high-risk patients. © 2014 by The American Society of Hematology.


Rawstron A.C.,St Jamess Institute of Oncology | Rawstron A.C.,University of York
Histopathology | Year: 2011

The term monoclonal B-cell lymphocytosis (MBL) was recently introduced to identify individuals with a population of monoclonal B cells in the absence of other features that are diagnostic of a B-cell lymphoproliferative disorder. MBL is often identified through hospital investigation of a mild lymphocytosis, and approximately 1% of such individuals develop progressive disease requiring treatment per year. However, in population studies using high-sensitivity flow cytometry, MBL may be detectable in more than 10% of adults aged over 60years, and clinical progression is rare. The majority of MBL cases have features that are characteristic of chronic lymphocytic leukaemia, but an increasing amount of information is becoming available about MBL with the features of other B-cell lymphoproliferative disorders. In addition to flow cytometry findings, the incidental detection of an occult B-cell lymphoproliferative disorder is also occurring in a significant proportion of tissue biopsy samples. In this review, the clinical and biological relationship between MBL and B-cell lymphoproliferative disorders will be discussed, with a focus on identifying the differences between low levels of peripheral blood or bone marrow involvement with lymphoma and the monoclonal B-cell populations that commonly occurr in elderly adults. © 2011 Blackwell Publishing Limited.


Bhatnagar P.,St Jamess Institute of Oncology | Subesinghe M.,St Jamess Institute of Oncology | Patel C.,St Jamess Institute of Oncology | Prestwich R.,St Jamess Institute of Oncology | Scarsbrook A.F.,St Jamess Institute of Oncology
Radiographics | Year: 2013

Patients with squamous cell carcinomas (SCCs) of the head and neck are increasingly treated nonsurgically. Imaging plays a critical role in helping define the targets for radiation therapy, especially intensity-modulated radiation therapy, in which the dose gradients are steep. Anatomic imaging with conventional modalities, particularly computed tomography (CT), has been used in patients with head and neck SCCs, but this approach has limitations. Functional imaging techniques, including positron emission tomography (PET) combined with CT or magnetic resonance (MR) imaging, offer complementary information and can be used noninvasively to assess a range of biomarkers in patients with head and neck SCCs, including hypoxia, cell proliferation and apoptosis, and epidermal growth factor receptor status. These biologic markers can be monitored before, during, and after treatment to improve patient selection for specific therapeutic strategies, guide adaptation of therapy, and potentially facilitate more accurate assessment of disease response. This article discusses the practical aspects of integrating functional imaging into head-and-neck radiation therapy planning and reviews the potential of molecular imaging biomarkers for response assessment and therapy adaptation. The uses of PET tracers for imaging cellular processes such as metabolism, proliferation, hypoxia, and cell membrane synthesis are explored, and applications for MR techniques such as dynamic contrast material-enhanced imaging, diffusion-weighted imaging, blood oxygenation level-dependent imaging, and MR spectroscopy are reviewed. The potential of integrated PET/CT perfusion imaging and hybrid PET/MR imaging also is highlighted. These developments may allow more individualized treatment planning in patients with head and neck SCCs in the emerging era of personalized medicine. © RSNA, 2013.


Prestwich R.J.,St Jamess Institute Of Oncology | Oksuz D.O.,St Jamess Institute Of Oncology | Dyker K.,St Jamess Institute Of Oncology | Coyle C.,St Jamess Institute Of Oncology | Sen M.,St Jamess Institute Of Oncology
International Journal of Radiation Oncology Biology Physics | Year: 2011

Purpose: To report the experience of treating selected fit patients with locally advanced head-and-neck squamous cell carcinoma with three cycles of induction TPF (docetaxel 75 mg/m 2, cisplatin 75 mg/m 2, 5-fluorouracil 750 mg/m 2, Days 2-5) followed by concurrent three-weekly bolus cisplatin 100 mg/m 2 chemoradiotherapy. Methods and Materials: Between March 2006 and February 2010, 66 patients with nonmetastatic Stage IV head-and-neck squamous cell carcinoma were treated in a single institution with three cycles of induction TPF, followed by radical radiotherapy with concurrent cisplatin 100 mg/m 2. Results: Median age was 54 years (range, 33-69 years). Median follow-up was 21 months (range, 4-55 months). During TPF, Grade 3 toxicity occurred in 18 patients (27%), dose modifications in 10 (15%), delays in 3 (5%), and unplanned admissions in 6 (9%); a clinical tumor response was documented in 60 patients (91%). Median time from the final cycle of TPF to commencing radiotherapy was 22 days. Sixty-two patients (94%) received radical radiotherapy, and all completed treatment with no delays ≥3 days. One, two, and three cycles of concurrent cisplatin were delivered to 18 patients (29%), 38 patients (61%), and 3 patients (5%), respectively. Ninety-two percent of patients received enteral feeding; median weight loss during treatment was 7%. Forty-two patients (68%) had unplanned admissions with no on-treatment deaths. Three unrelated deaths occurred after treatment. At 1 year after treatment, 21% of patients without disease progression remained gastrostomy dependent. Of 58 assessable patients, 50 (86%) achieved a complete response after treatment. One- and 2-year progression-free survival, cause-specific survival, and overall survival were 88%, 92%, and 86% and 80%, 85%, and 80%, respectively. Conclusion: The combination of induction TPF with concurrent cisplatin chemoradiotherapy in patients with locally advanced head and neck squamous cell carcinoma is tolerable, with encouraging efficacy. © 2011 Elsevier Inc.


Taylor N.,University of Sheffield | Absolom K.,St Jamess Institute of Oncology | Snowden J.,Royal Hallamshire Hospital | Eiser C.,University of Sheffield
European Journal of Cancer Care | Year: 2012

Follow-up is recommended for survivors of childhood cancer. Decisions about care tend to be made in terms of physical health, but psychological late effects including post-traumatic stress disorder (PTSD) and symptoms (PTSS) are prevalent. We report prevalence of PTSD/PTSS in a UK cohort, self-care and implications for organisation of follow-up. Eligible survivors (n= 218) under regular follow-up were invited to complete measures of PTSD, late effects and self-efficacy. Information about late effects was also taken from medical notes. A total of 118 survivors responded (54.1%) and 108 (49.5%) completed questionnaires. Prevalence of clinical PTSD (13.9%) was comparable with US findings. Female subjects and those who reported more late effects reported more PTSD. In regression analyses, number of survivor-reported late effects (but not number-recorded in medical notes) and PTSS predicted self-efficacy. Significant numbers of survivors report PTSS but this is unrelated to diagnosis or treatment. Female subjects and those who reported more physical late effects also reported more PTSS. Decisions to discharge survivors from routine care must consider psychological well-being as well as physical late effects. We recommend routine psychological screening for all survivors of childhood cancer and suggest this can be acceptable to survivors and feasible in clinic. © 2011 Blackwell Publishing Ltd.


Owen R.G.,St Jamess Institute of Oncology
Clinical lymphoma, myeloma & leukemia | Year: 2011

Histological transformation, typically to diffuse large B-cell lymphoma (DLBCL) is reported to occur in 5%-10% of patients with WM and recent studies have highlighted a possible aetiological role for the nucleoside analogues. It is however becoming increasingly clear that histological transformation is a complex phenomenon and may include clonally unrelated disorders. In order to highlight this pathological heterogeneity we describe 5 patients with diverse histological progression events. These included EBV-associated events namely DLBCL, peripheral T-cell lymphoma and spontaneously resolving mucocutaneous ulcer. A further 2 patients demonstrated a localised plasma cell rich lesion simulating plasmacytoma and a de novo DLBCL arising in an unrelated B-cell clone. It is clear therefore that detailed pathological assessments are required in all suspected cases of transformation and that the pathological heterogeneity demonstrated by this study needs to be taken into account when potential aetiological factors are being assessed. Copyright © 2010 Elsevier Inc. All rights reserved.


In chronic lymphocytic leukemia (CLL) the level of minimal residual disease (MRD) after therapy is an independent predictor of outcome. Given the increasing number of new agents being explored for CLL therapy, using MRD as a surrogate could greatly reduce the time necessary to assess their efficacy. In this European Research Initiative on CLL (ERIC) project we have identified and validated a flow-cytometric approach to reliably quantitate CLL cells to the level of 0.0010% (10-5). The assay comprises a core panel of six markers (i.e. CD19, CD20, CD5, CD43, CD79b and CD81) with a component specification independent of instrument and reagents, which can be locally re-validated using normal peripheral blood. This method is directly comparable to previous ERIC-designed assays and also provides a backbone for investigation of new markers. A parallel analysis of high-throughput sequencing using the ClonoSEQ assay showed good concordance with flow cytometry results at the 0.010% (10-4) level, the MRD threshold defined in the 2008 International Workshop on CLL guidelines, but it also provides good linearity to a detection limit of 1 in a million (10-6). The combination of both technologies would permit a highly sensitive approach to MRD detection while providing a reproducible and broadly accessible method to quantify residual disease and optimize treatment in CLL.Leukemia advance online publication, 29 January 2016; doi:10.1038/leu.2015.313. © 2015 Macmillan Publishers Limited


Spencer J.A.,St Jamess Institute Of Oncology | Ghattamaneni S.,St Jamess Institute Of Oncology
Radiology | Year: 2010

Magnetic resonance (MR) imaging of the sonographically indeterminate adnexal mass can be used to guide patient care and reduce the costs of investigation and treatment. Most indeterminate masses result from common benign conditions, and women with such masses can avoid unnecessary or inappropriate surgery. For the minority of women in whom indeterminate masses are malignant, use of MR imaging rather than a "wait and watch" strategy of interval re-examination with ultrasonography offers a more timely diagnosis. There are simple diagnostic steps in the MR imaging assessment that direct a problem-solving, tailored approach based on signal characteristics and morphology. © RSNA, 2010.


Rawstron A.C.,St Jamess Institute Of Oncology | Rawstron A.C.,University of York | Hillmen P.,St Jamess Institute Of Oncology
Best Practice and Research: Clinical Haematology | Year: 2010

Monoclonal B-lymphocytosis (MBL) is defined as the presence of a population of monoclonal B-cells, usually with a chronic lymphocytic leukaemia (CLL) phenotype, which comprise fewer than 5000 cells per μl with no evidence of tissue involvement. Over the past few years, MBL has been clearly defined and differentiated from CLL so that individuals with MBL are no longer inappropriately labelled as suffering from leukaemia. In this review, we will describe the entity of MBL and summarise the evidence that underlies the current theory on the pathophysiology of the disorder, the relationship with CLL and the probability of developing progressive disease requiring treatment. In addition, we will evaluate the importance of further clinical investigations, in particular, the relevance of screening for MBL and undertaking bone marrow investigations according to the clinical setting and B-cell phenotype. © 2010 Elsevier Ltd. All rights reserved.

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