• Effect of epoetin alfa on survival and cancer treatment-related anemia and fatigue in patients receiving radical radiotherapy with curative intent for head and neck cancer.

      Hoskin, Peter J; Robinson, Martin; Slevin, Nicholas J; Morgan, David; Harrington, Kevin; Gaffney, Christopher; Marie Curie Research Wing for Oncology, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex, UK. peterhoskin@nhs.net (2009-12-01)
      PURPOSE: To evaluate the effect of epoetin alfa on local disease-free survival (DFS), overall survival (OS), and cancer treatment-related anemia and fatigue in patients with head and neck cancer receiving radical radiotherapy with curative intent. PATIENTS AND METHODS: Patients (N = 301) with hemoglobin (Hb) less than 15 g/dL were randomly assigned in a ratio of 1:1 to receive radiotherapy plus epoetin alfa (10,000 U subcutaneously [SC] three times weekly if baseline Hb was < 12.5 g/dL; 4,000 U SC three times weekly if baseline Hb > or = 12.5 g/dL) or radiotherapy alone. Hb levels were monitored weekly. The primary end point was local DFS, defined as the time from random assignment to local disease recurrence or death. Secondary efficacy end points included OS, local tumor response, and local tumor control. Patients were followed at 1, 4, 8, and 12 weeks postradiotherapy and annually for 5 years. Cancer treatment-related anemia and fatigue were evaluated with the Functional Assessment of Cancer Therapy-Anemia and Functional Assessment of Cancer Therapy-Head and Neck. Adverse events were recorded up to 12 weeks postradiotherapy. RESULTS: Hb levels increased from baseline with epoetin alfa. The median duration of local DFS was not statistically different between groups (observation, 35.42 months; epoetin alfa, 31.47 months; hazard ratio, 1.04; 95% CI, 0.77 to 1.41). Groups did not significantly differ in DFS, OS, tumor outcomes, or cancer treatment-related anemia or fatigue. No new or unexpected adverse events were observed. CONCLUSION: Addition of epoetin alfa to radical radiotherapy did not affect survival, tumor outcomes, anemia, or fatigue positively or negatively in patients with head and neck cancer.
    • Effectiveness of a home care nursing program in the symptom management of patients with colorectal and breast cancer receiving oral chemotherapy: a randomized, controlled trial.

      Molassiotis, Alexander; Brearley, Sarah; Saunders, Mark P; Craven, Olive; Wardley, Andrew M; Farrell, Carole; Swindell, Ric; Todd, Chris; Luker, Karen; University of Manchester, School of Nursing, University Place, Manchester, M13 9PL, United Kingdom. alex.molassiotis@manchester.ac.uk (2009-12-20)
      PURPOSE: To assess the effectiveness of a symptom-focused home care program in patients with cancer who were receiving oral chemotherapy in relation to toxicity levels, anxiety, depression, quality of life, and service utilization. PATIENTS AND METHODS: A randomized, controlled trial was carried out with 164 patients with a diagnosis of colorectal (n = 110) and breast (n = 54) cancers who were receiving oral capecitabine. Patients were randomly assigned to receive either a home care program by a nurse or standard care for 18 weeks (ie, six cycles of chemotherapy). Toxicity assessments were carried out weekly for the duration of the patients' participation in the trial, and validated self-report tools assessed anxiety, depression, and quality of life. RESULTS: Significant improvements were observed in the home care group in relation to the symptoms of oral mucositis, diarrhea, constipation, nausea, pain, fatigue (first four cycles), and insomnia (all P < .05). This improvement was most significant during the initial two cycles. Unplanned service utilization, particularly the number of inpatient days (57 v 167 days; P = .02), also was lower in the home care group. CONCLUSION: A symptom-focused home care program was able to assist patients to manage their treatment adverse effects more effectively than standard care. It is imperative that patients receiving oral chemotherapy are supported with such programs, particularly during initial treatment cycles, to improve their treatment and symptom experiences.
    • Endometrial adenocarcinoma: an analysis of treatment and outcome.

      Byrd, Louise M; Swindell, Ric; Webber-Rookes, Daniel; Hannon, Robert; Hunter, Robin D; Livsey, Jacqueline E; Davidson, Susan E; Department of Obstetrics and Gynaecology, St Mary's Hospital for Women and Children, Manchester, UK. louise.byrd@cmmc.nhs.uk (2008-11)
      This study aims to review the survival and morbidity in patients treated for endometrial cancer, at a single centre and analyses the effects of co-morbidity on these outcomes. Case notes of all patients referred to the Christie Hospital with endometrial carcinoma from January 1, 1993 to December 31, 1995 (n=499) were reviewed. Twenty patients presented with recurrence and were not included in this analysis. Three hundred and seventy-five patients had previously undergone a total abdominal hysterectomy and bilateral salpingoophorectomy (+/- pelvic lymphadenectomy). Of these, 175 received adjuvant external beam radiotherapy (XRT) only, 49 received XRT and brachytherapy, 30 received brachytherapy alone and 121 patients had no further therapy. One hundred and four patients were referred for primary treatment. Radical radiotherapy was administered to 63 patients who were unfit for surgery, with 10 of these receiving XRT + brachytherapy and 53 receiving brachytherapy alone. Thirteen patients received palliative XRT and 28 supportive care only. The overall 5-year survival for those treated radically was 73.3%. There was no significant survival difference between patients who underwent surgery and adjuvant radiotherapy, in whatever form (p=0.115). Patients who did not undergo surgery did less well as a group, although there was no significant survival difference between those treated with combination therapy or brachytherapy alone (p=0.33). Survival was significantly associated with FIGO stage, tumour grade, age (especially those >75 years) and co-morbidity (ACE-27 score). Late morbidity occurred in 46 patients, with severe toxicity affecting 12 (3.8%). Toxicity was associated with ACE-27 score (p=0.0019), treatment dose and modality, with 50% (n=6) of severe toxicity seen in patients receiving adjuvant XRT + ICT. These data demonstrate that survival in patients with endometrial carcinoma treated radically remains good, with the stage and grade of tumour being significant factors for overall survival. The incidence of severe morbidity related to radiotherapy of any modality was 3.8%. A high co-morbidity (ACE-27) score was significantly associated with poorer survival (p<0.0055) and increased late treatment morbidity (p=0.0019).
    • ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy).

      Brunelli, A; Charloux, Anne; Bolliger, C T; Rocco, G; Sculier, J-P; Varela, G; Licker, M; Ferguson, M K; Faivre-Finn, Corinne; Huber, R M; et al. (2009-07)
      A collaboration of multidisciplinary experts on the functional evaluation of lung cancer patients has been facilitated by the European Respiratory Society (ERS) and the European Society of Thoracic Surgery (ESTS), in order to draw up recommendations and provide clinicians with clear, up-to-date guidelines on fitness for surgery and chemo-radiotherapy. The subject was divided into different topics, which were then assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. The draft reports written by the experts on each topic were reviewed, discussed and voted on by the entire expert panel. The evidence supporting each recommendation was summarised, and graded as described by the Scottish Intercollegiate Guidelines Network Grading Review Group. Clinical practice guidelines were generated and finalized in a functional algorithm for risk stratification of the lung resection candidates, emphasising cardiological evaluation, forced expiratory volume in 1 s, systematic carbon monoxide lung diffusion capacity and exercise testing. Contrary to lung resection, for which the scientific evidences are more robust, we were unable to recommend any specific test, cut-off value, or algorithm before chemo-radiotherapy due to the lack of data. We recommend that lung cancer patients should be managed in specialised settings by multidisciplinary teams.
    • Estimation of renal function -- what is appropriate in cancer patients?

      Barraclough, Lisa H; Field, Catherine; Wieringa, Gilbert E; Swindell, Ric; Livsey, Jacqueline E; Davidson, Susan E; Department of Clinical Oncology, Christie Hospital, Manchester, UK. lisahelenbone@hotmail.com (2008-12)
      AIMS: To compare the accuracy of renal assessment in patients with cancer using radioisotope glomerular filtration rate (GFR), urine collection for creatinine clearance, Cockroft-Gault, Modification of Diet in Renal Disease (MDRD) and Wright formulae. MATERIALS AND METHODS: Measurements of isotope GFR from 367 patients were compared with estimates from the described methods (Cockroft-Gault, MDRD, Wright). An analysis including a further 252 patients with an isotope GFR < or = 50 ml/min was also carried out. RESULTS: The Wright formula was the most accurate form of estimating renal function for the first study group. The formulae were similar in accuracy in the second study group. CONCLUSIONS: The Wright formula is the most accurate form of estimation of renal function in comparison with the isotope GFR for cancer patients. When there is a large proportion of patients with a low isotope GFR (< or = 50 ml/min), the formulae have similar accuracy.
    • European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.

      Rafnar, T; Vermeulen, S H; Sulem, P; Thorleifsson, G; Aben, Katja K H; Witjes, J A; Grotenhuis, A J; Verhaegh, G W; Hulsbergen-van de Kaa, C A; Besenbacher, S; et al. (2011-11-01)
      Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.
    • The European Respiratory Society and European Society of Thoracic Surgeons clinical guidelines for evaluating fitness for radical treatment (surgery and chemoradiotherapy) in patients with lung cancer.

      Brunelli, Alessandro; Charloux, Anne; Bolliger, Chris T; Rocco, Gaetano; Sculier, Jean-Paul; Varela, Gonzalo; Licker, Marc; Ferguson, Mark K; Faivre-Finn, Corinne; Huber, Rudolf Maria; et al. (2009-07)
      The European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS) established a joint task force with the purpose to develop clinical evidence-based guidelines on evaluation of fitness for radical therapy in patients with lung cancer. The following topics were discussed, and are summarized in the final report along with graded recommendations: Cardiologic evaluation before lung resection; lung function tests and exercise tests (limitations of ppoFEV1; DLCO: systematic or selective?; split function studies; exercise tests: systematic; low-tech exercise tests; cardiopulmonary (high tech) exercise tests); future trends in preoperative work-up; physiotherapy/rehabilitation and smoking cessation; scoring systems; advanced care management (ICU/HDU); quality of life in patients submitted to radical treatment; combined cancer surgery and lung volume reduction surgery; compromised parenchymal sparing resections and minimally invasive techniques: the balance between oncological radicality and functional reserve; neoadjuvant chemotherapy and complications; definitive chemo and radiotherapy: functional selection criteria and definition of risk; should surgical criteria be re-calibrated for radiotherapy?; the patient at prohibitive surgical risk: alternatives to surgery; who should treat thoracic patients and where these patients should be treated?
    • Evaluation of educational methods in dermatology and confidence levels: a national survey of UK medical students.

      Chiang, Yi Zhen; Tan, Kian Tjon; Chiang, Yi Ning; Burge, Susan M; Griffiths, Christopher E M; Verbov, Julian L; Department of Medicine, Salford Royal National Health Service Foundation Trust, Manchester, UK. chiangyizhen@gmail.com (2011-02)
      The high prevalence of skin conditions makes dermatology education an essential part of the undergraduate medical curriculum. The aim of this study was to assess the impact of different educational methods on confidence levels in dermatology among UK medical students.
    • Evidence for extrathyroidal formation of 3-iodothyronamine in humans as provided by a novel monoclonal antibody-based chemiluminescent serum immunoassay.

      Hoefig, C S; Köhrle, J; Brabant, Georg E; Dixit, Kashinath C S; Yap, Beng K; Strasburger, C J; Wu, Z; Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany. (2011-06)
      Thyronamines are thyronergic metabolites of thyroid hormones. Lack of reliable and sensitive detection methods for endogenous 3-iodothyronamine (3-T(1)AM) has so far hampered progress in understanding their physiological action and role in endocrine homeostasis or pathophysiology of diseases.
    • External beam boost for cancer of the cervix uteri when intracavitary therapy cannot be performed.

      Barraclough, Lisa H; Swindell, Ric; Livsey, Jacqueline E; Hunter, Robin D; Davidson, Susan E; Department of Clinical Oncology, Christie Hospital, Manchester, UK. lisahelenbone@hotmail.com (2008-07-01)
      PURPOSE: To assess the outcome of patients treated with radical radiotherapy for cervical cancer who received an external beam boost, in place of intracavitary brachytherapy (ICT), after irradiation to the whole pelvis. METHODS AND MATERIALS: Case notes were reviewed for all patients treated in this way in a single center between 1996 and 2004. Patient and tumor details, the reasons why ICT was not possible, and treatment outcome were documented. RESULTS: Forty-four patients were identified. The mean age was 56.4 years (range, 26-88 years). Clinical International Federation of Gynecology and Obstetrics or radiologic stage for Stages I, II, III, and IV, respectively, was 16%, 48%, 27%, and 7%. A total radiation dose of 54-70 Gy was given (75% received > or =60 Gy). Reasons for ICT not being performed were technical limitations in 73%, comorbidity or isolation limitations in 23%, and patient choice in 4%. The median follow-up was 2.3 years. Recurrent disease was seen in 48%, with a median time to recurrence of 2.3 years. Central recurrence was seen in 16 of the 21 patients with recurrent disease. The 5-year overall survival rate was 49.3%. The 3-year cancer-specific survival rate by stage was 100%, 70%, and 42% for Stages I, II, and III, respectively. Late Grades 1 and 2 bowel, bladder, and vaginal toxicity were seen in 41%. Late Grade 3 toxicity was seen in 2%. CONCLUSION: An external beam boost is a reasonable option after external beam radiotherapy to the pelvis when it is not possible to perform ICT.
    • EXTRA--a multicenter phase II study of chemoradiation using a 5 day per week oral regimen of capecitabine and intravenous mitomycin C in anal cancer.

      Glynne-Jones, Rob; Meadows, Helen; Wan, Susan; Gollins, Simon W; Leslie, Martin; Levine, Edward; McDonald, Alec C; Myint, A Sun; Samuel, Les; Sebag-Montefiore, David; et al. (2008-09-01)
      PURPOSE: 5-Fluorouracil (5-FU) + mitomycin C (MMC)-based chemoradiotherapy is standard treatment for patients with epidermoid anal carcinoma. Clinical trials in other cancers have confirmed 5-FU can successfully be replaced by the oral fluoropyrimidine capecitabine. This phase II trial aimed to determine the feasibility, toxicity, and efficacy of capecitabine, MMC and radiotherapy (RT) in anal cancer patients. METHODS AND MATERIALS: Radiotherapy comprised the schedule of the UK Anal Cancer Trial (ACT) II trial (50.4 Gy in 28 fractions of 1.8 Gy). With MMC (12 mg/m2) on Day 1 and capecitabine on each RT treatment day in two divided doses (825 mg/m2 b.i.d). The endpoints were complete response at 4 weeks, local control at 6 months and toxicity. RESULTS: Thirty-one patients entered the trial. The median age was 61 years (range 45-86) with 14 males and 17 females. Compliance with chemotherapy with no dose interruptions or delays was 68%, and with RT was 81%. Eighteen (58%) patients completed both modalities of treatment as planned. Dose-limiting Grade 3 or 4 diarrhea was seen in 1 of 31 patients. Three patients experienced Grade 3 neutropenia. There were no treatment-related deaths. Four weeks following completion of chemoradiation, 24 patients (77%) had a complete clinical response, and 4 (16%) a partial response. With a median follow-up of 14 months, three locoregional relapses occurred. CONCLUSIONS: Capecitabine with MMC and RT in with patients anal carcinoma is well tolerated, with minimal toxicity and acceptable compliance. We recommend testing this schedule in future national Phase III studies in anal cancer.
    • Gastrointestinal symptoms after pelvic radiotherapy: a national survey of gastroenterologists.

      Henson, Caroline C; Davidson, Susan E; Lalji, A; Symonds, R P; Swindell, Ric; Andreyev, H J; Department of Radiotherapy Related Research, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK, caroline.henson@christie.nhs.uk. (2011-11-13)
      PURPOSE: Seventeen thousand patients receive treatment with radical pelvic radiotherapy annually in the UK. Up to 50% develop significant gastrointestinal symptoms. The National Cancer Survivorship Initiative has identified access to specialist medical care for those with complications after cancer as one of their four key needs. We aimed to determine the current practice of British gastroenterologists with regards to chronic gastrointestinal symptoms after pelvic radiotherapy. METHODS: A questionnaire was developed and sent up to a maximum of five times to all UK consultant gastroenterologists. RESULTS: Eight hundred sixty-six gastroenterologists were approached and 165 (20%) responded. Sixty-one percent saw one to four patients annually with bowel symptoms after radiotherapy. Eighteen percent rate the current treatments as effective "often" or "most of the time". Forty-seven percent of gastroenterologists consider themselves "confident with basic cases", with 11% "confident in all cases". Fifty-nine percent thinks a gastroenterologist with a specialist interest should manage these patients. Although only 29% thinks a specific service is required for these patients, 34% rates the current service as inadequate. The ideal service was considered to be gastroenterology-led, multidisciplinary and regional. Low referral rates, poor evidence-base and poor funding are cited as reasons for the current patchy services. CONCLUSIONS: The low response rate contrasts with that from a parallel survey of clinical oncologists. This may reflect the opinion that radiation-induced bowel toxicity is not a significant issue, which may be because only a small proportion of patients are referred to gastroenterologists. The development of new, evidence-based gastroenterology-led services is considered the optimal way to meet the needs of these patients.
    • Guidelines for preclinical and early phase clinical assessment of novel radiosensitisers.

      Harrington, K J; Billingham, L J; Brunner, T B; Burnet, N G; Chan, C S; Hoskin, P; Mackay, Ranald I; Maughan, T S; Macdougall, J; McKenna, W G; et al. (2011-08-23)
    • Guidelines on the investigation and management of follicular lymphoma.

      McNamara, C; Davies, J; Dyer, M; Hoskin, P; Illidge, Timothy M; Lyttelton, M; Marcus, R; Montoto, S; Ramsay, A; Wong, W L; et al. (2012-02)
    • Guidelines on the radical management of patients with lung cancer.

      Lim, E; Baldwin, D; Beckles, M; Duffy, J; Entwisle, J; Faivre-Finn, Corinne; Kerr, K; Macfie, A; McGuigan, J; Padley, S; et al. (2010-10)
      A joint initiative by the British Thoracic Society and the Society for Cardiothoracic Surgery in Great Britain and Ireland was undertaken to update the 2001 guidelines for the selection and assessment of patients with lung cancer who can potentially be managed by radical treatment.
    • Hand function after high dose rate brachytherapy for squamous cell carcinoma of the skin of the hand.

      Somanchi, B V; Stanton, Anthony; Webb, M; Loncaster, Juliette A; Allan, Ernest; Muir, L T S W; Department of Hand Surgery, Salford Royal Hospital, Salford M6 8HD, UK. brindavihari2001@yahoo.com (2008-11)
      AIMS: Current recommendations for the treatment of squamous cell carcinoma of the hand are almost unanimously in favour of ablative surgery. However, many of the patients are frail and elderly, and surgical techniques frequently involve skin grafts or amputation of digits. A non-invasive method of treatment is, therefore, often preferred. Radiotherapy using a brachytherapy technique is a well-established option. This study investigated whether patients found the treatment acceptable and assessed the outcome of treatment in terms of local control, cosmesis and hand function. MATERIALS AND METHODS: Twenty-five patients who underwent mould brachytherapy using a microselectron high dose rate radiotherapy device were available for assessment. We assessed the functional status of the hand and fingers by means of the Disability of Arm, Shoulder and Hand and Michigan Hand Outcomes questionnaires. We examined the hand to assess the severity of post-radiation stigmata. We enquired as to patient acceptability of treatment and outcome. RESULTS: Of 25 patients who agreed to participate, the fingers were affected in 15 and the dorsum of the hand in 10. The mean age at the time of radiotherapy was 69 years (range 50-87). There were no significant differences in parameters, such as range of motion of fingers and wrist, hand/finger grip strength, between the treated and opposite sides. Sensation, including two-point discrimination, was not significantly different from the untreated hand. Seventeen patients had minor skin changes. No patient found the treatment painful or unacceptable. Twenty patients were very satisfied and five patients were moderately satisfied with the cosmetic result. CONCLUSIONS: We conclude that high dose rate brachytherapy is a safe and simple alternative to surgical treatment for squamous cell carcinoma of the hand, as it is not only successful in eradicating tumour, but also preserves hand function.
    • Hoechst 33342 side population identification is a conserved and unified mechanism in urological cancers.

      Oates, Jeremy E; Grey, Benjamin R; Addla, Sanjai K; Samuel, Joanne D; Hart, Claire A; Ramani, Vijay A C; Brown, Michael D; Clarke, Noel W; Genito-Urinary Cancer Research Group, School of Cancer and Imaging Sciences, Paterson Institute for Cancer Research, Manchester M20 4BX, United Kingdom. jez_oates@hotmail.com (2009-12)
      Mutation within the adult human stem cell (SC) compartment has been proposed as a factor in the initiation and promotion of carcinogenesis. Isolation of these cancer stem cells (CSCs) has proven difficult, limiting their subsequent phenotypic, functional, and genetic characterization. We have used the Hoechst 33342 dye efflux technique to isolate an epithelial side population (SP) from genitourinary (GU) cancers, which is enriched for cells with SC traits. With informed consent, samples were taken from patients with primary tumors and undergoing surgery for prostatic (CaP), invasive bladder transitional cell (TCC), and renal cell carcinomas (RCC). Single cell epithelial suspensions were extracted from these and incubated with Hoechst 33342. Hoechst SP/non-SP profiles were then generated by flow cytometry using standardized protocols. SP/non-SP cell cycle status was established by Hoechst 33342 and Pyronin Y staining. Immunocytochemistry staining was performed for markers suggested as stem markers as well as lineage-specific markers. Functionality was determined using colony-forming assays and long-term monolayer culture. A characteristic verapamil-sensitive SP was isolated from all 3 urological malignancies and represented 0.57% +/- 0.11% (CaP), 0.52% +/- 0.49% (TCC), and 5.9% +/- 0.9% (RCC) of the total epithelial population. Cell cycle analysis showed that the SP had enhanced numbers of cells in G(0) as compared to the total cell population (CaP 12.4% +/- 3.2 vs. 3.8% +/- 1.0, RCC 23.2% +/- 3.4 vs. 1.8% +/- 0.9, and TCC 28.5% +/- 4.9 vs. 4% +/- 1.3). Immunocytochemistry demonstrated an increased expression of proliferative and putative stem markers within the SP fraction. Cultures confirmed significant enhancement of colony-forming ability and proliferative capacity of the SP fraction. A characteristic SP enriched for stem-like cells has been isolated from the 3 most common urological malignancies. This provides strong evidence that Hoechst 33342 efflux is a conserved and unified mechanism in GU cancer.
    • How have outcomes for patients with follicular lymphoma changed with the addition of monoclonal antibodies?

      Illidge, Timothy M; Chan, Clara; School of Cancer and Imaging Sciences, University of Manchester, Manchester, UK. tmi@manchester.ac.uk (2008-07)
      The outcome for patients with follicular lymphoma (FL) has substantially improved over the last few years. This improved survival appears to be largely related to the increasingly widespread use of anti-CD20 monoclonal antibody (mAb) rituximab in the therapy of FL today, either in combination with chemotherapy, for remission 'induction' and more recently as 'maintenance' therapy. Encouraging results have also been reported from radiolabelled anti-CD20 mAb or radioimmunotherapy (RIT), which exploits the unique method of action of this approach and high radiosensitivity of FL. High response rates and durable remissions have been seen with both (90)Y Ibritumomab tiuxetan and (131)I Tositumomab, and more recently compelling data are emerging demonstrating the efficacy of using these drugs as consolidation after initial treatment with chemotherapy or rituximab plus chemotherapy combinations. This review will focus on the current approaches and explore the data that has led to the emergence of a new nomenclature appearing in the language of clinicians involved in the treatment of FL, namely 'induction' therapy, 'consolidation' of initial response and 'maintenance' therapy. The current treatment approaches that have led to such increased optimism regarding the therapeutic outcome in FL are evaluated and discussed.
    • Hypofractionated Intensity-Modulated Radiotherapy for Carcinoma of the Prostate: Analysis of Toxicity.

      Coote, Joanna H; Wylie, James P; Cowan, Richard A; Logue, John P; Swindell, Ric; Livsey, Jacqueline E; Department of Clinical Oncology, Christie Hospital, Manchester, United Kingdom. (2009-01-06)
      PURPOSE: Dose escalation for prostate cancer improves biological control but with a significant increase in late toxicity. Recent estimates of low alpha/beta ratio for prostate cancer suggest that hypofractionation may result in biological advantage. Intensity-modulated radiotherapy (IMRT) should enable dose escalation to the prostate while reducing toxicity to local organs. We report late toxicity data of a hypofractionated IMRT regime. METHODS AND MATERIALS: Eligible men had T2-3N0M0 adenocarcinoma prostate, and either Gleason score >/= 7 or prostate-specific antigen 20-50 ng/L. Patients received 57-60 Gy to prostate in 19-20 fractions using five-field IMRT. All received hormonal therapy for 3 months before radiotherapy to a maximum of 6 months. Toxicity was assessed 2 years postradiotherapy using the RTOG criteria, LENT/SOMA, and UCLA prostate index assessment tools. RESULTS: Acute toxicity was favorable with no RTOG Grade 3 or 4 toxicity. At 2 years, there was 4% Grade 2 bowel and 4.25% Grade 2 bladder toxicity. There was no Grade 3 or 4 bowel toxicity; one patient developed Grade 3 bladder toxicity. UCLA data showed a slight improvement in urinary function at 2 years compared with pretreatment. LENT/SOMA assessments demonstrated general worsening of bowel function at 2 years. Patients receiving 60 Gy were more likely to develop problems with bowel function than those receiving 57 Gy. CONCLUSIONS: These data demonstrate that hypofractionated radiotherapy using IMRT for prostate cancer is well tolerated with minimal late toxicity at 2 years posttreatment. Ongoing studies are looking at the efficacy of hypofractionated regimes with respect to biological control.
    • The impact of lymphovascular invasion on survival in oral carcinoma.

      Jones, H B; Sykes, Andrew J; Bayman, Neil A; Sloan, Philip; Swindell, Ric; Patel, M; Musgrove, Brian; Maxillofacial Unit, Wythenshawe Hospital, Southmoor Rd, Wythenshawe, Manchester, United Kingdom M239LT. huwbjones@tiscali.co.uk (2009-01)
      Data was retrospectively analysed on 72 consecutive patients treated primarily with resection and concomitant neck dissection for intraoral carcinomas. Twenty prognostic variables were assessed by univariate analysis to assess their influence on survival. Seven variables were significant at the 5% level. Survival was negatively influenced by six tumour related factors, increasing T stage (P=0.039), increasing N stage (P=0.004), greater than two nodes histologically positive nodal disease (P=0.017), tumour size > 4 cm (P=0.022), residual disease at the primary site (P=0.012), extracapsular nodal spread (P=0.01) and the one treatment related factor analysed, adjuvant radiotherapy (P=0.039). Subsequent multivariate analysis was performed via the cox stepwise regression method to assess the influence on survival of all factors which achieved significance at the 20% level. There were only two variables which made a significant difference (P<0.05) to the multivariate model. The presence of lymphovascular invasion (P=0.015) and histological evidence of mandibular invasion (P=0.047). Lymphovascular invasion appeared in the final model despite not achieving statistical significance at the 5% level on univariate analysis. A final cox survival model was constructed. The relative risk of death for those with cervical metastases (N2 and above) at diagnosis was 3.74 (P=0.005). The addition of lymphovascular invasion to the cox model revealed an increase in the relative risk of death in the presence of lymphovascular invasion of 2.99 (P=0.015). Patients with nodal negative disease and one single node positive provided the baseline risk as there was no significant difference between these two groups. The presence of histological evidence of lymphovascular invasion in oral carcinoma surgical specimens has a significant impact on survival outcome in oral carcinoma patients.