• 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.
    • The impact of radiotherapy late effects on quality of life in gynaecological cancer patients.

      Barker, Claire L; Routledge, Jacqueline A; Farnell, Damian J J; Swindell, Ric; Davidson, Susan E; Department of Clinical Oncology, the Christie NHS Foundation Trust, Manchester, UK. claire.barker@doctors.org.uk (2009-05-19)
      The aims of this study were to assess changes in quality of life (QoL) scores in relation to radical radiotherapy for gynaecological cancer (before and after treatment up to 3 years), and to identify the effect that late treatment effects have on QoL. This was a prospective study involving 225 gynaecological cancer patients. A QoL instrument (European Organisation for the Research and Treatment of Cancer QLQ-C30) and late treatment effect questionnaire (Late Effects Normal Tissues - Subjective Objective Management Analysis) were completed before and after treatment (immediately after radiotherapy, 6 weeks, 12, 24 and 36 months after treatment). Most patients had acute physical symptoms and impaired functioning immediately after treatment. Levels of fatigue and diarrhoea only returned to those at pre-treatment assessment after 6 weeks. Patients with high treatment toxicity scores had lower global QoL scores. In conclusion, treatment with radiotherapy for gynaecological cancer has a negative effect on QoL, most apparent immediately after treatment. Certain late treatment effects have a negative effect on QoL for at least 2 years after radiotherapy. These treatment effects are centred on symptoms relating to the rectum and bowel, for example, diarrhoea, tenesmus and urgency. Future research will identify specific symptoms resulting from late treatment toxicity that have the greatest effect on QoL; therefore allowing effective management plans to be developed to reduce these symptoms and improve QoL in gynaecological cancer patients.
    • The impact of radiotherapy on swallowing and speech in patients who undergo total laryngectomy.

      De Casso, Carmen; Slevin, Nicholas J; Homer, Jarrod J; University Department of Otolaryngology-Head and Neck Surgery, Manchester Royal Infirmary, Manchester, UK. cdecasso@doctors.org.uk (2008-12)
      OBJECTIVES: Quality of life studies have shown no detrimental effect with radiotherapy (RT) in patients who have a total laryngectomy. We wished to determine the effect of RT (initial or postoperative) specifically on the swallowing and voice function in patients treated by total laryngectomy (TL) for carcinoma of the larynx. DESIGN: Multicenter chart review. SETTING: Multicenter study in the Greater Manchester and Lancashire area. PARTICIPANTS: A total of 121 postlaryngectomy patients all of whom had completed definitive treatment at least 6 months before this study. Twenty-six patients had total laryngectomy as a single modality treatment and 95 had total laryngectomy and radiotherapy. MAIN OUTCOME MEASURES: Swallowing (solid food, soft diet or fluid/PEG) and voice development. RESULTS: Swallowing was better in the group who had no radiotherapy (P = 0.0037). There was no difference in voice function between the two groups. We also demonstrated that females had a worse swallowing outcome (P = 0.0101), as did advanced nodal stage (P = 0.001). CONCLUSIONS: RT adversely affects the swallowing results but not the speech results after TL when given either as initial treatment or postoperatively. This should be kept in mind in the decision-making process in the treatment of patients with carcinoma of the larynx.
    • Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials.

      Renehan, Andrew G; Egger, Matthias; Saunders, Mark P; O'Dwyer, Sarah T; Department of Surgery, Christie Hospital NHS Trust, Manchester M20 4BX. arenehan@picr.man.ac.uk (2002-04-06)
      OBJECTIVE: To review the evidence from clinical trials of follow up of patients after curative resection for colorectal cancer. DESIGN: Systematic review and meta-analysis of randomised controlled trials of intensive compared with control follow up. MAIN OUTCOME MEASURES: All cause mortality at five years (primary outcome). Rates of recurrence of intraluminal, local, and metastatic disease and metachronous (second colorectal primary) cancers (secondary outcomes). RESULTS: Five trials, which included 1342 patients, met the inclusion criteria. Intensive follow up was associated with a reduction in all cause mortality (combined risk ratio 0.81, 95% confidence interval 0.70 to 0.94, P=0.007). The effect was most pronounced in the four extramural detection trials that used computed tomography and frequent measurements of serum carcinoembryonic antigen (risk ratio 0.73, 0.60 to 0.89, P=0.002). Intensive follow up was associated with significantly earlier detection of all recurrences (difference in means 8.5 months, 7.6 to 9.4 months, P<0.001) and an increased detection rate for isolated local recurrences (risk ratio 1.61, 1.12 to 2.32, P=0.011). CONCLUSIONS: Intensive follow up after curative resection for colorectal cancer improves survival. Large trials are required to identify which components of intensive follow up are most beneficial.
    • Improving survival with thoracic radiotherapy in patients with small cell lung cancer. The CONVERT and the REST Trials.

      Faivre-Finn, Corinne; Blackhall, Fiona H; Snee, Michael; Harden, S; Hulse, Paul; Lorigan, Paul C (2010-09)
    • IMRT dose fractionation for head and neck cancer: variation in current approaches will make standardisation difficult.

      Ho, Kean F; Fowler, Jack F; Sykes, Andrew J; Yap, Beng K; Lee, Lip W; Slevin, Nicholas J; Academic Department of Radiation Oncology, University of Manchester, Christie Hospital, Wilmslow Road, Manchester, UK. (2009)
      INTRODUCTION: Altered fractionation has demonstrated clinical benefits compared to the conventional 2 Gy/day standard of 70 Gy. When using synchronous chemotherapy, there is uncertainty about optimum fractionation. IMRT with its potential for Simultaneous Integrated Boost (SIB) adds further to this uncertainty. This survey will examine international practice of IMRT fractionation and suggest possible reasons for diversity in approach. MATERIAL AND METHODS: Fourteen international cancer centres were surveyed for IMRT dose/fractionation practised in each centre. RESULTS: Twelve different types of dose fractionation were reported. Conventional 70-72 Gy (daily 2 Gy/fraction) was used in 3/14 centres with concurrent chemotherapy while 11/14 centres used altered fractionation. Two centres used >1 schedule. Reported schedules and number of centres included 6 fractions/week DAHANCA regime (3), modest hypofractionation (< or =2.2 Gy/fraction) (3), dose-escalated hypofractionation (> or =2.3 Gy/fraction) (4), hyperfractionation (1), continuous acceleration (1) and concomitant boost (1). Reasons for dose fractionation variability include (i) dose escalation; (ii) total irradiated volume; (iii) number of target volumes; (iv) synchronous systemic treatment; (v) shorter overall treatment time; (vi) resources availability; (vii) longer time on treatment couch; (viii) variable GTV margins; (ix) confidence in treatment setup; (x) late tissue toxicity and (xi) use of lower neck anterior fields. CONCLUSIONS: This variability in IMRT fractionation makes any meaningful comparison of treatment results difficult. Some standardization is needed particularly for design of multi-centre randomized clinical trials.
    • Inconsistencies in the care of head and neck cancer patients experiencing trismus.

      Lee, Rana; Slevin, Nicholas J; The Christie Hospital NHS Foundation Trust, Manchester (2011-09)
    • Inter-fraction motion and dosimetric consequences during breast intensity-modulated radiotherapy (IMRT).

      Jain, Pooja; Marchant, Thomas E; Green, Melanie M; Watkins, Gillian R; Davies, Julie; McCarthy, Claire; Loncaster, Juliette A; Stewart, Alan L; Magee, Brian; Moore, Christopher J; et al. (2009-01)
      BACKGROUND AND PURPOSE: Intensity-modulated radiotherapy (IMRT) can improve dose homogeneity within the breast planned target volume (PTV), but may be more susceptible to patient/organ motion than standard tangential radiotherapy (RT). We used daily cone-beam CT (CBCT) imaging to assess inter-fraction motion during breast IMRT and its subsequent impact on IMRT and standard RT dose homogeneity. MATERIALS AND METHODS: Ten breast cancer patients selected for IMRT were studied. CBCT images were acquired immediately after daily treatment. Automatic image co-registration was used to determine patient positioning variations. Daily PTV contours were used to calculate PTV variations and daily delivered IMRT and theoretically planned tangential RT dose. RESULTS: Group systematic (and random) setup errors detected by CBCT were 5.7 (3.9)mm laterally, 2.8 (3.5)mm vertically and 2.3 (3.2)mm longitudinally. Rotations >2 degrees in any axis occurred on 53/106 (50%) occasions. Daily PTV volume varied up to 23%. IMRT dose homogeneity was superior at planning and throughout the treatment compared with standard RT (1.8% vs. 15.8% PTV received >105% planned mean dose), despite increased motion sensitivity. CONCLUSIONS: CBCT revealed inadequacies of current patient positioning and verification procedures during breast RT and confirmed improved dose homogeneity using IMRT for the patients studied.
    • Irinotecan+5-fluorouracil with concomitant pre-operative radiotherapy in locally advanced non-resectable rectal cancer: a phase I/II study.

      Iles, S M; Gollins, Simon W; Susnerwala, Shabbir; Haylock, B; Myint, A Sun; Biswas, A; Swindell, Ric; Levine, Edward; Department of Clinical Oncology, The Christie Hospital NHS Trust, Manchester M20 4BX, UK. (2008-04-08)
      In the UK, 10% of patients diagnosed with rectal cancer have inoperable disease at presentation. This study ascertained whether the resectability rate of inoperable locally advanced rectal cancer was improved by administration of intravenous irinotecan, 5-fluorouracil (5-FU) and pelvic radiotherapy. During phase I of the trial (n=12), the dose of irinotecan was escalated in three-patient cohorts from 50 mg m(-2) to 60 mg m(-2) to 70 mg m(-2) to identify the maximum tolerated dose (60 mg m(-2)). In phase II, 31 patients with non-resectable disease received 45 Gy radiotherapy and 5-FU infusions (200 mg m(-2) per day) for 5 weeks. Irinotecan (60 mg m(-2)) was given on days 1, 8, 15 and 22. After treatment, patients were operated on if possible. Thirty patients completed the protocol, 28 underwent surgery. Before surgery, MRI restaging of 24 patients showed that 19 (79%) had a reduction in tumour stage after treatment (seven complete clinical response and 12 partial). Of 27 patients followed up after surgery, 22 (81%) had clear circumferential resection margins. Disease-free and overall survival estimates at 3 years were 65 and 90%, respectively. The regimen was well tolerated. Irinotecan, 5-FU and radiotherapy results in tumour downgrading, allowing resection of previously inoperable tumour with acceptable toxicity.