• Non-standard radical treatment of skin cancer.

      McPartlin, Andrew J; Slevin, Nicholas J; The Christie Hospital NHS Foundation Trust, Manchester (2011-09)
    • A novel imaging technique for fusion of high-quality immobilised MR images of the head and neck with CT scans for radiotherapy target delineation.

      Webster, Gareth J; Kilgallon, J E; Ho, Kean F; Rowbottom, Carl G; Slevin, Nicholas J; Mackay, Ranald I; North Western Medical Physics, Christie Hospital NHS Foundation Trust, Manchester, UK. gareth.webster@physics.cr.man.ac.uk (2009-06)
      Uncertainty and inconsistency are observed in target volume delineation in the head and neck for radiotherapy treatment planning based only on CT imaging. Alternative modalities such as MRI have previously been incorporated into the delineation process to provide additional anatomical information. This work aims to improve on previous studies by combining good image quality with precise patient immobilisation in order to maintain patient position between scans. MR images were acquired using quadrature coils placed over the head and neck while the patient was immobilised in the treatment position using a five-point thermoplastic shell. The MR image and CT images were automatically fused in the Pinnacle treatment planning system using Syntegra software. Image quality, distortion and accuracy of the image registration using patient anatomy were evaluated. Image quality was found to be superior to that acquired using the body coil, while distortion was < 1.0 mm to a radius of 8.7 cm from the scan centre. Image registration accuracy was found to be 2.2 mm (+/- 0.9 mm) and < 3.0 degrees (n = 6). A novel MRI technique that combines good image quality with patient immobilization has been developed and is now in clinical use. The scan duration of approximately 15 min has been well tolerated by all patients.
    • Omitting elective nodal irradiation during thoracic irradiation in limited-stage small cell lung cancer - Evidence from a phase II trial.

      Colaco, Rovel J; Sheikh, Hamid Y; Lorigan, Paul C; Blackhall, Fiona H; Hulse, Paul; Califano, Raffaele; Ashcroft, Linda; Taylor, Paul; Thatcher, Nick; Faivre-Finn, Corinne; et al. (2012-04)
      Omitting elective nodal irradiation (ENI) in limited-stage disease small cell lung cancer (LD-SCLC) is expected to result in smaller radiation fields. We report on data from a randomised phase II trial that omitted ENI in patients receiving concurrent chemo-radiotherapy for LD-SCLC. 38 patients with LD-SCLC were randomised to receive once-daily (66Gy in 33 fractions) or twice-daily (45Gy in 30 fractions) radiotherapy (RT). 3D-conformal RT was given concurrently with cisplatin and etoposide starting with the second cycle of a total of four cycles. The gross tumour volume was defined as primary tumour with involved lymph nodes (nodes ≥1cm in short axis) identifiable with CT imaging. ENI was not used. Six recurrence patterns were identified: recurrence within planning target volume (PTV) only, recurrence within PTV+regional nodal recurrence and/or distant recurrence, isolated nodal recurrence outside PTV, nodal recurrence outside PTV+distant recurrence, distant metastases only and no recurrence. At median follow-up 16.9 months, 31/38 patients were evaluable and 14/31 patients had relapsed. There were no isolated nodal recurrences. Eight patients relapsed with intra-thoracic disease: 2 within PTV only, 4 within PTV and distantly and 2 with nodal recurrence outside PTV plus distant metastases. Rates of grade 3+ acute oesophagitis and pneumonitis in the 31 evaluable patients were 23 and 3% respectively. In our study of LD-SCLC, omitting ENI based on CT imaging was not associated with a high risk of isolated nodal recurrence, although further prospective studies are needed to confirm this. Routine ENI omission will be further evaluated prospectively in the ongoing phase III CONVERT trial (NCT00433563).
    • Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial.

      Nutting, C; Morden, J; Harrington, K; Urbano, Teresa G; Bhide, S A; Clark, C; Miles, E A; Miah, A B; Newbold, K; Tanay, M A; et al. (2011-02)
      Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia.
    • Patterns of relapse following radiotherapy for differentiated thyroid cancer: implication for target volume delineation.

      Azrif, Muhammad; Slevin, Nicholas J; Sykes, Andrew J; Swindell, Ric; Yap, Beng K; Department of Clinical Oncology, Christie Hospital, Manchester, United Kingdom. (2008-10)
      INTRODUCTION: Post-operative residual disease in differentiated thyroid cancer is an indication for external beam radiotherapy (EBRT) especially if there is poor radioiodine uptake by the residual disease. There are no standardized guidelines or consensus in target delineation for radiotherapy in thyroid cancer. AIMS: To determine the pattern of recurrence in patients with well differentiated thyroid cancer who received adjuvant or definitive radiotherapy as well as radioiodine ablation following surgery or biopsy with a view to better defining future target volume delineation for radiotherapy. MATERIALS AND METHODS: Forty-nine patients with differentiated thyroid cancer received radical external beam radiotherapy and radioiodine ablation (3.5GBq) following thyroidectomy or biopsy between 1990 and 2000. Nineteen patients had macroscopic residual (11) or inoperable disease (8), whilst 30 patients had clear (5) or microscopic positive resection margin (24), and 1 patient the resection margin status was unknown. All the patients were deemed high risk for local recurrence or progressive disease. The thyroid bed and regional nodes were irradiated using two radiotherapy techniques: (1) non co-planar lateral fields (NCLF) in coronal plane using 6MV photons to a dose of 45-50Gy in 16 fractions over 22 days and (2) anterior-posterior parallel pair of 6MV photons to a dose of 40-42.5Gy in 16 fractions over 22 days. There was no attempt to irradiate the lymph nodes in that part of the anterior and posterior mediastinum extending from the brachiocephalic veins to the carina. RESULTS: The median follow-up was 5.4 years (range 0.9-12.4 years). The actuarial 5-year cause-specific survival and local control for the whole group was 75.7% and 81.4%, respectively. Of the 4 patients with mediastinal recurrence, all had neck recurrences and two had distant metastases. All the medisastinal recurrences occurred in superior mediastinum (level VII) and all were treated with NCLF in coronal plane radiotherapy technique. Furthermore, mediastinal recurrences did not occur in isolation. The 5-years loco-regional control rate was 89.1% for those with clear or microscopic positive margins and 69.2% for those with macroscopic residual or inoperable disease. Five-year cause specific survival was 58.3% for patients with macroscopic residual or inoperable disease and 91.4% for those with clear or microscopic positive margins. CONCLUSION: The status of postoperative margin relating to bulk of disease influences local control and cause specific survival. Surgical resection in locally advanced thyroid cancer should be performed by an experienced surgeon to achieve macroscopic clearance where possible. The majority of recurrences were loco-regional. The few superior mediastinal recurrences did not occur in isolation. All the mediastinal recurrences occurred in the superior mediastinum (level VII). We recommend the target volume should encompass the thyroid bed and regional neck nodes and the superior mediastinum level VII excluding the lymph nodes on both sides of the trachea within the anterior and posterior mediastinum extending from the brachiocephalic veins to the carina (compartment 4). Thus, this should facilitate dose escalation to improve loco-regional control and avoiding radiation induced mediastinal toxicity.
    • Pharmacokinetic and tolerability profile of once-daily zibotentan (ZD4054) in Japanese and Caucasian patients with hormone-resistant prostate cancer.

      Ranson, Malcolm R; Wilson, R H; O'Sullivan, J M; Maruoka, M; Yamaguchi, A; Cowan, Richard A; Logue, John P; Tomkinson, H; Tominaga, N; Swaisland, H; et al. (2010-11)
      Objective: To investigate potential differences in zibotentan pharmacokinetics between Japanese and Caucasian patients with hormone-resistant prostate cancer (HRPC) following single and multiple dosing. Methods: In the Japanese study, 18 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 26 days' once-daily dosing. In the Caucasian study, 21 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 12 days' once-daily dosing. Results: Pharmacokinetic parameters were similar between populations. Absorption of zibotentan was rapid with maximum plasma concentrations typically achieved within 3 h of dosing. Mean clearance, 17.9 and 18.7 ml/min in Japanese and Caucasian patients, respectively (range 7.0 - 36.3 ml/min in Japanese patients and 7.8 - 29.5 ml/min in Caucasian patients) and volume of distribution, 14.0 and 15.6 l for Japanese and Caucasian patients, respectively (range 7.9 - 29.1 l in Japanese patients and 9.6 - 23.8 l in Caucasian patients) were relatively low, and t1/2 was approximately 12 h (range 5.7 - 18.8 h in Japanese patients and 5.0 - 22.9 h in Caucasian patients) following single dosing. Little accumulation was observed following daily dosing and multiple-dose pharmacokinetics were predictable. Exposure levels achieved in some Japanese patients receiving zibotentan 15 mg were higher than those observed in Caucasian patients, however, this may be due to differences in body weight, as exposure levels were similar when data were normalized for body weight. Zibotentan was well tolerated in both populations. Conclusions: There are no clinically relevant differences in the disposition and pharmacokinetics of zibotentan between Japanese and Caucasian patients with HRPC.
    • A phase I study of the safety and pharmacokinetics of the combination of pertuzumab (rhuMab 2C4) and capecitabine in patients with advanced solid tumors.

      Albanell, Joan; Montagut, Clara; Jones, Eileen T; Pronk, Linda; Mellado, Begoña; Beech, Janette; Gascon, Pere; Zugmaier, Gerhard; Brewster, Michael; Saunders, Mark P; et al. (2008-05-01)
      PURPOSE: To study the safety, pharmacokinetics, and recommended dose of the combination of pertuzumab, a humanized monoclonal antibody HER2-dimerization inhibitor, and capecitabine in patients with advanced malignancies. EXPERIMENTAL DESIGN: Patients that had progressed to standard treatment were treated with pertuzumab at a fixed dose of 1,050 mg given i.v. on day 1 plus capecitabine at doses of 825-1,000-1,250 mg/m(2), twice daily orally on days 1 to 14 of each 21-day treatment cycle, in three sequential cohorts. The pharmacokinetics of capecitabine and pertuzumab were studied. Patients received a single dose of capecitabine in a pretreatment phase (day -7) followed by serum sampling for capecitabine and its metabolites. RESULTS: Nineteen patients were accrued and 18 were assessable. The combination of capecitabine and pertuzumab was well tolerated at all dose levels and no dose-limiting toxicities were observed. The most frequent adverse event was asthenia, which was grade 3 in two patients. One asymptomatic pulmonary embolism occurred. No other grade 3 or 4 adverse events or cardiac or left ventricular ejection fraction events were reported. There was no apparent change in the pharmacokinetics of capecitabine and its metabolites when combined with pertuzumab. The pharmacokinetics of pertuzumab was apparently not modified when administered with capecitabine. Disease stabilization was observed in 11 patients. CONCLUSIONS: Pertuzumab and capecitabine were well tolerated at all dose levels. Escalation beyond the highest dose level tested was not planned, as this included the recommended doses of monotherapy for both drugs. In conclusion, this combination is ready for phase II testing.
    • A phase II study evaluating the use of concurrent mitomycin C and capecitabine in patients with advanced unresectable pseudomyxoma peritonei.

      Farquharson, Adam L; Pranesh, Nagarajan; Witham, Gary; Swindell, Ric; Taylor, Malcolm B; Renehan, Andrew G; Rout, Shantanu; Wilson, Malcolm S; O'Dwyer, Sarah T; Saunders, Mark P; et al. (2008-08-19)
      Pseudomyxoma peritonei (PMP) is a rare neoplastic process characterised by progressive intra-abdominal dissemination of mucinous tumour, and generally considered resistant to systemic chemotherapy. A phase II study in patients with advanced unresectable PMP was undertaken to evaluate the combination of systemic concurrent mitomycin C (7 mg m(-2) i.v. on day 1) and capecitabine (1250 mg m(-2) b.d. on days 1-14) in a 3-weekly cycle (MCap). Response was determined by semiquantitative assessment of disease volume on serial computed tomographic (CT) scans and serum tumour marker (CEA, CA125, CA19-9) changes at 12 weeks. Between 2003 and 2006, 40 patients were recruited through a national centre for the treatment of peritoneal surface tumours. At baseline, 23 patients had progressive disease and 17 had stable disease. Of 39 assessable patients, 15 (38%, 95% confidence intervals (CIs): 25, 54%) benefited from chemotherapy in the form of either reductions in mucinous deposition or stabilisation of progressive pretreatment disease determined on CT scan. Notably, two patients, originally considered unresectable, following MCap and re-staging underwent potentially curative cytoreductive surgery. Grade 3/4 toxicity rates were low (6%, 95% CIs: 4, 9%). Twenty out of 29 assessed patients (69%, 95% CIs: 51, 83%) felt that their Global Health Status improved during chemotherapy. This is the first trial to demonstrate an apparent benefit of systemic chemotherapy in patients with advanced unresectable PMP.
    • Phase II study of cisplatin and imatinib in advanced salivary adenoid cystic carcinoma.

      Ghosal, N; Mais, Kathleen L; Shenjere, Patrick; Julyan, Peter J; Hastings, David L; Ward, Timothy H; Ryder, W David J; Bruce, I; Homer, Jarrod J; Slevin, Nicholas J; et al. (2011-10)
      Patients with adenoid cystic carcinoma of the salivary glands show over-expression of KIT in a high proportion of cases. Options for systemic treatment are limited in locally advanced and metastatic disease. We explored the efficacy of imatinib and cisplatin combined in this group of patients. A Gehan's two-stage, phase II trial was conducted on 28 patients. Those with progressive, locally advanced, and metastatic disease with an over-expression of KIT were treated with single agent imatinib 800 mg daily for two months, followed by a combination of imatinib 400mg daily and cisplatin 80 mg/m(2) at four-weekly intervals for six cycles. This was followed by maintenance single agent imatinib 400mg daily until the disease progressed. Response was monitored using fluorodeoxyglucose positron emission tomography (FDG-PET) and morphological imaging using computed tomography, magnetic resonance, and chest radiographs (CT/MRI/CXR). Morphological imaging showed partial response in three of 28 patients, and five patients showed a response on FDG-PET. In addition, 19 patients had useful stabilisation of disease. The median time to progression and overall survival was 15 months (range 1-43) and 35 months (range 1-75), respectively. The combination of imatinib and cisplatin was reasonably well tolerated. This combination may provide stabilisation in locally advanced and metastatic adenoid cystic carcinoma of the salivary glands.
    • Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer.

      Baka, Sofia; Califano, Raffaele; Ferraldeschi, Roberta; Ashcroft, Linda; Thatcher, Nick; Taylor, Pat; Faivre-Finn, Corinne; Blackhall, Fiona H; Lorigan, Paul C; Department of Medical Oncology, Christie Hospital NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK. (2008-08-05)
      This randomised trial compared platinum-based to anthracycline-based chemotherapy in patients with small-cell lung cancer (limited or extensive stage) and
    • Point: why choose pulsed-dose-rate brachytherapy for treating gynecologic cancers?

      Davidson, Susan E; Hendry, Jolyon H; West, Catharine M L; Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom. Susan.Davidson@christie.nhs.uk (2010-08-09)
    • Prediction of post-treatment trismus in head and neck cancer patients.

      Lee, Rana; Slevin, Nicholas J; Musgrove, Brian; Swindell, Ric; Molassiotis, Alexander; Christie Hospital NHS Trust, Manchester M20 4BX, UK. (2011-07-25)
      Our aim was to establish the incidence of trismus over time, together with risk factors (including quality of life (QoL)) for the prediction of trismus after treatment in patients with cancer of the head and neck. It was a longitudinal study of 152 patients accepted for primary operation who attended the head and neck cancer clinic of a tertiary referral cancer centre in the United Kingdom. A total of 87 patients was studied prospectively. Our results showed that 41/87 (47%) of patients presented with trismus, 57/80 (71%) had postoperative trismus, and 41/52 (79%) had trismus 6 months after operation or radiotherapy (trismus defined as a maximum mouth opening of ≤35mm). Men and those who drank a lot of alcohol were less likely to have trismus after treatment. QoL variables showed that pain, eating, chewing, taste, saliva, social functioning, social contact, and dry mouth were significantly more impaired in the trismus group than among those without trismus. Postoperative differences in QoL between the two groups highlighted problems with social function and role-playing, fatigue, activity, recreation, and overall reduction in QoL. Women, and those who do not drink alcohol, are at particularly high risk of developing trismus, and, to prevent it and treat it, patients may benefit from multidisciplinary management at an early stage during treatment.
    • Preoperative chemoradiotherapy using concurrent capecitabine and irinotecan in magnetic resonance imaging-defined locally advanced rectal cancer: impact on long-term clinical outcomes.

      Gollins, S; Sun Myint, A; Haylock, Brian; Wise, M; Saunders, Mark P; Neupane, R; Essapen, S; Samuel, L; Dougal, Mark; Lloyd, A; et al. (2011-03-10)
      To assess long-term clinical outcomes of preoperative chemoradiotherapy of magnetic resonance imaging (MRI)-defined locally advanced rectal adenocarcinoma using concurrent irinotecan and capecitabine.
    • Preoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2).

      Gollins, Simon W; Myint, S; Susnerwala, S; Haylock, B; Wise, M; Topham, C; Samuel, L; Swindell, Ric; Morris, J; Mason, L; et al. (2009-09-15)
      BACKGROUND: The aim of this study was to investigate the safety of neoadjuvant chemoradiation using radiotherapy (RT) combined with concurrent capecitabine and irinotecan for locally advanced rectal cancer before surgery. METHODS: Forty-six patients were recruited and treated on the basis that MRI scanning had shown poor-risk tumours with threatening (< or =1 mm) or involvement of the mesorectal fascia. Conformal RT was given using 3 or 4 fields at daily fractions of 1.8 Gy on 5 days per week to a total dose of 45 Gy. Concurrently oral capecitabine was given twice daily throughout radiotherapy continuously from days 1 to 35 and intravenous irinotecan was given once per week during weeks 1 to 4 of RT. Dose levels were gradually escalated as follows. Dose level 1: capecitabine 650 mg m(-2) b.i.d. and irinotecan 50 mg m(-2); Dose level 2: capecitabine 650 mg m(-2) b.i.d. and irinotecan 60 mg m(-2); Dose level 3: capecitabine 825 mg m(-2) b.i.d. and irinotecan 60 mg m(2); Dose level 4: capecitabine 825 mg m(-2) b.i.d. and irinotecan 70 mg m(-2). RESULTS: Diarrhoea (grade 3, no grade 4) was the main serious acute toxicity with lesser degrees of fatigue, neutropenia, anorexia and palmar-plantar erythrodysesthesia. The recommended dose for future study was dose level 2 at which 3 of 14 patients (21%) developed grade 3 diarrhoea. Postoperative complications included seven pelvic or wound infections and two anastomotic and two perineal wound dehiscences. There were no deaths in the first 30 days postoperatively. Of 41 resected specimens, 11 (27%) showed a pathological complete response (pCR) and five (12%) showed an involved circumferential resection margin (defined as < or =1 mm). The 3-year disease-free survival (intent-to-treat) was 53.2%. CONCLUSION: In patients with poor-risk MRI-defined locally advanced rectal cancer threatening or involving the mesorectal fascia, preoperative chemoradiation based on RT at 45 Gy in 25 daily fractions over 5 weeks with continuous daily oral capecitabine at 650 mg m(-2) b.i.d. days 1-35 and weekly IV irinotecan at 60 mg m(-2) weeks 1-4, provides acceptable acute toxicity and postoperative morbidity with encouraging response and curative resection rates.
    • Preoperative neo-adjuvant therapy for curable rectal cancer--reaching a consensus 2008.

      Scott, N A; Susnerwala, Shabbir; Gollins, Simon W; Myint, A Sun; Levine, Edward; Department of Colorectal Surgery, Lancashire Teaching Hospital Trust, Preston, UK. nigel.scott@lthtr.nhs.uk (2009-03)
      OBJECTIVE: Our aim was to determine the range of neo-adjuvant therapy the multidisciplinary team (MDT) currently offers patients with curable (M(0)) rectal cancer. METHOD: A senior oncologist from each of the four oncology centres in north Wales and the north-west of England (approximate target population 8 million - Glan Clwyd, Clatterbridge, Christie and Preston) reviewed his/her understanding of the current evidence of neo-adjuvant therapy in rectal cancer. Then a representative from each centre was asked to identify which of three neo-adjuvant options (no neo-adjuvant therapy, short-course radiotherapy 25 Gy over five fractions and long-course chemoradiotherapy) he/she would use for a rectal cancer in the upper, middle or lower third of the rectum staged by magnetic resonance imaging as being T(2)-T(4) and/or N(0)-N(2). RESULTS: In all cases of locally advanced rectal cancer (T(3a) N(1)-T(4)), oncologists from the four oncology centres recommended long-course chemoradiotherapy before rectal resection. This consensus was maintained for cases of lower third T(3a) N(0) cancers. Thereafter, the majority of patients with rectal cancer are offered adjuvant short-course radiotherapy. CONCLUSION: Neo-adjuvant therapy is less likely to be offered if the tumour is early (T(2), N(0)) and/or situated in the upper third of the rectum.
    • Primary Radiotherapy for Carcinoma of the Retromolar Trigone; A Useful Alternative to Surgery.

      Bayman, Neil A; Sykes, Andrew J; Bonington, Suzanne C; Blackburn, T; Patel, M; Swindell, Ric; Slevin, Nicholas J; Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK. (2009-12-03)
      AIMS: Squamous cell carcinoma of the retromolar trigone is uncommon. The standard initial treatment is primary surgery, which usually involves microvascular reconstruction with a composite flap. Some patients are considered unsuitable for this procedure. This retrospective study examined the outcome and toxicity for patients with squamous cell carcinoma of the retromolar trigone treated with definitive radiotherapy in a single centre. MATERIALS AND METHODS: Between 1991 and 2000, 43 patients were treated with definitive radiotherapy with a median dose of 50Gy in 16 fractions over 21 days. Hospital case notes and radiotherapy records were analysed. RESULTS: The median age was 66 years (range 39-84 years). Nodal disease was evident in 13 (30.2%) patients. Twenty-one patients (51.2%) had stage I/II disease and 20 patients (48.8%) had stage III/IV disease. After a median follow-up of 59 months, 13 (30.2%) patients were alive and well, nine (20.9%) patients had died of an intercurrent illness and 21 (48.8%) had died of their disease. Five-year locoregional control was 46.5% (95% confidence interval 29.7-61.7), cause-specific survival was 45.7% (95% confidence interval 29.1-60.8) and overall survival was 30.9% (95% confidence interval 17.5-46.3). Osteoradionecrosis was documented in two patients. DISCUSSION: This hypofractionated regimen is convenient for this patient population and produced comparable outcomes to longer fractionation schedules without an increase in late toxicity.
    • Prophylactic cranial irradiation in extensive disease small-cell lung cancer: short-term health-related quality of life and patient reported symptoms: results of an international Phase III randomized controlled trial by the EORTC Radiation Oncology and Lung Cancer Groups.

      Slotman, Berend J; Mauer, Murielle E; Bottomley, Andrew; Faivre-Finn, Corinne; Kramer, Gijs; Rankin, Elaine M; Snee, Michael; Hatton, Matthew; Postmus, Pieter E; Collette, Laurence; et al. (2009-01-01)
      PURPOSE: Prophylactic cranial irradiation (PCI) in patients with extensive-disease small-cell lung cancer (ED-SCLC) leads to significantly fewer symptomatic brain metastases and improved survival. Detailed effects of PCI on health-related quality of life (HRQOL) are reported here. PATIENTS AND METHODS: Patients (age, 18 to 75 years; WHO < or = 2) with ED-SCLC, and any response to chemotherapy, were randomly assigned to either observation or PCI. Health-related quality of life (HRQOL) and patient-reported symptoms were secondary end points. The European Organisation for the Research and Treatment of Cancer core HRQOL tool (Quality of Life Questionnaire C30) and brain module (Quality of Life Questionnaire Brain Cancer Module) were used to collect self-reported patient data. Six HRQOL scales were selected as primary HRQOL end points: global health status; hair loss; fatigue; and role, cognitive and emotional functioning. Assessments were performed at random assignment, 6 weeks, 3 months, and then 3-monthly up to 1 year and 6-monthly thereafter. RESULTS: Compliance with the HRQOL assessment was 93.7% at baseline and dropped to 60% at 6 weeks. Short-term results up to 3 months showed that there was a negative impact of PCI on selected HRQOL scales. The largest mean difference between the two arms was observed for fatigue and hair loss. The impact of PCI on global health status as well as on functioning scores was more limited. For global health status, the observed mean difference was eight points on a scale 0 to 100 at 6 weeks (P = .018) and 3 months (P = .055). CONCLUSION: PCI should be offered to all responding ED SCLC patients. Patients should be informed of the potential adverse effects from PCI. Clinicians should be alert to these; monitor their patients; and offer appropriate support, clinical, and psychosocial care.
    • Prophylactic radiotherapy to intervention sites in mesothelioma: a systematic review and survey of UK practice.

      Lee, Caroline; Bayman, Neil A; Swindell, Ric; Faivre-Finn, Corinne; Department of Clinical Oncology, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. (2009-11)
      BACKGROUND AND PURPOSE: Patients with malignant pleural mesothelioma (MPM), who undergo chest instrumentation, may develop seeding at the site of intervention, leading to subcutaneous tumour. This is believed to be reduced by the common practice of prophylactic irradiation to intervention tracts (PIT). However, evidence to support PIT is currently inadequate and contentious. MATERIALS AND METHODS: We carried out a systematic search of published literature for articles relating to the incidence of chest wall intervention tract metastases and the use of PIT in mesothelioma. In addition, a survey of current practice was conducted in 54 UK oncology centres. RESULTS: Fourteen studies revealed an incidence of chest wall intervention tract metastases of 0-48% with a trend toward a higher rate of metastases for more invasive procedures. Three randomised controlled trials (RCTs), two prospective non-randomised studies and five retrospective series met the eligibility criteria to evaluate the role of PIT in MPM. Of the three RCTs, two did not support the use of PIT. None of the RCTs included patients who had received systemic chemotherapy. Of the oncology centres responding to the survey, 75% practiced PIT, and 80% would be interested in a trial to determine the efficacy of PIT. CONCLUSIONS: No consensus has been reached to support the use of PIT. However, most centres in the UK still offer PIT. There was widespread interest in a randomised controlled trial to establish PIT efficacy in the era of effective systemic chemotherapy for malignant pleural mesothelioma.
    • A prospective observational study of chemotherapy-related nausea and vomiting in routine practice in a UK cancer centre.

      Molassiotis, Alexander; Saunders, Mark P; Valle, Juan W; Wilson, Gregory; Lorigan, Paul C; Wardley, Andrew M; Levine, Edward; Cowan, Richard A; Loncaster, Juliette A; Rittenberg, C; et al. (2008-02)
      OBJECTIVE: The aim of the study was to assess levels of chemotherapy-induced nausea and vomiting (CINV) in routine practice. MATERIALS AND METHODS: The study was an observational prospective evaluation using patient self-reports. One hundred and two patients with cancer in a single cancer centre in UK receiving their first chemotherapy treatment participated in the study and were followed up over four cycles, providing a total of 272 assessments of nausea and vomiting. Data was collected with the use of the MASCC Antiemesis Tool (MAT), which is an eight-item short clinical scale assessing acute and delayed nausea and vomiting after chemotherapy. RESULTS: Results indicated that acute vomiting was experienced by 15.7% of the patients in cycle 1 and delayed vomiting by 14.7%, while acute nausea was present in 37.3% of the patients and delayed nausea in 47.1%, increasing over the subsequent cycles. Moderately emetogenic and highly emetogenic chemotherapy had the highest incidence of CINV, whereas patients receiving highly emetogenic chemotherapy showed significant levels of delayed nausea. Acute symptoms were more easily controlled than delayed symptoms. DISCUSSION: The data suggest that, while vomiting is well controlled, nausea remains a significant problem in practice, and optimal management of CINV is yet to be achieved. Understanding more clearly the biological basis of nausea will assist in managing this complex symptom more effectively in practice.
    • Protocol for the combined immunosuppression & radiotherapy in thyroid eye disease (CIRTED) trial: A multi-centre, double-masked, factorial randomised controlled trial.

      Rajendram, Rathie; Lee, Richard W J; Potts, Mike J; Rose, Geoff E; Jain, Rajni; Olver, Jane M; Bremner, Fion; Hurel, Steven; Cook, Anne; Gattamaneni, Rao; et al. (2008)
      ABSTRACT: BACKGROUND: Medical management of thyroid eye disease remains controversial due to a paucity of high quality evidence on long-term treatment outcomes. Glucocorticoids are known to be effective initially but have significant side-effects with long-term use and recrudescence can occur on cessation. Current evidence is conflicting on the efficacy of radiotherapy and non-steroid systemic immunosuppression, and the majority of previous studies have been retrospective, uncontrolled, small or poorly designed.The Combined Immunosuppression and Radiotherapy in Thyroid Eye Disease (CIRTED) trial was designed to investigate the efficacy of radiotherapy and azathioprine in combination with a standard course of oral prednisolone in patients with active thyroid eye disease. METHODS/DESIGN: Patients with active thyroid eye disease will be randomised to receive (i) azathioprine or oral placebo and (ii) radiotherapy or sham-radiotherapy in this multi-centre, factorial randomised control trial. The primary outcome is improvement in disease severity (assessed using a composite binary measure) at 12 months and secondary end-points include quality of life scores and health economic measures. DISCUSSION: The CIRTED trial is the first study to evaluate the role of radiotherapy and azathioprine as part of a long-term, combination immunosuppressive treatment regime for Thyroid Eye Disease. It will provide evidence for the role of radiotherapy and prolonged immunosuppression in the management of this condition, as well as pilot data on their use in combination. We have paid particular attention in the trial design to establishing (a) robust placebo controls and masking protocols which are effective and safe for both radiotherapy and the systemic administration of an antiproliferative drug; (b) constructing effective inclusion and exclusion criteria to select for active disease; and (c) selecting pragmatic outcome measures. TRIAL REGISTRATION: Current controlled trials ISRCTN22471573.