• Management of hyponatraemia.

      Mittal, Rahul; Sheftel, H; Demssie, Y; Christie Hospital NHS Foundation Trust, Manchester, UK. (2011-02)
      Hyponatraemia (serum sodium level < 135 mmol/litre) is the most common electrolyte abnormality among hospitalized patients. A prevalence rate as high as 15-30% has been reported among patients admitted to acute and intensive care units (Hoorn et al, 2004; Jaber et al, 2006). Evidence suggests an increase in mortality associated with even a mild degree of hyponatraemia (Waikar et al, 2009). Besides its significance as a potential cause of morbidity and mortality, hyponatraemia could also serve as a useful indicator for undiagnosed underlying pathology such as endocrine disorders or malignancy. A systematic approach towards the clinical assessment and interpretation of biochemical abnormalities is vital to facilitate the diagnosis and management of hyponatraemia. The optimal treatment of hyponatraemia should take into account its severity, duration and mode of clinical presentation. Overzealous correction could result in irreversible neurological complications.
    • Management of the lymph nodes in penile cancer.

      Heyns, Chris F; Fleshner, Neil; Sangar, Vijay K; Schlenker, Boris; Yuvaraja, Thyavihally B; Van Poppel, Hendrik; Department of Urology, Stellenbosch University and Tygerberg Hospital, Tygerberg, South Africa. cfh2@sun.ac.za (2010-08)
      A comprehensive literature study was conducted to evaluate the levels of evidence (LEs) in publications on the diagnosis and staging of penile cancer. Recommendations from the available evidence were formulated and discussed by the full panel of the International Consultation on Penile Cancer in November 2008. The final grades of recommendation (GRs) were assigned according to the LE of the relevant publications. The following consensus recommendations were accepted. Fine needle aspiration cytology should be performed in all patients (with ultrasound guidance in those with nonpalpable nodes). If the findings are positive, therapeutic, rather than diagnostic, inguinal lymph node dissection (ILND) can be performed (GR B). Antibiotic treatment for 3-6 weeks before ILND in patients with palpable inguinal nodes is not recommended (GR B). Abdominopelvic computed tomography (CT) and magnetic resonance imaging (MRI) are not useful in patients with nonpalpable nodes. However, they can be used in those with large, palpable inguinal nodes (GR B). The statistical probability of inguinal micrometastases can be estimated using risk group stratification or a risk calculation nomogram (GR B). Surveillance is recommended if the nomogram probability of positive nodes is <0.1 (10%). Surveillance is also recommended if the primary lesion is grade 1, pTis, pTa (verrucous carcinoma), or pT1, with no lymphovascular invasion, and clinically nonpalpable inguinal nodes, but only provided the patient is willing to comply with regular follow-up (GR B). In the presence of factors that impede reliable surveillance (obesity, previous inguinal surgery, or radiotherapy) prophylactic ILND might be a preferable option (GR C). In the intermediate-risk group (nomogram probability .1-.5 [10%-50%] or primary tumor grade 1-2, T1-T2, cN0, no lymphovascular invasion), surveillance is acceptable, provided the patient is informed of the risks and is willing and able to comply. If not, sentinel node biopsy (SNB) or limited (modified) ILND should be performed (GR B). In the high-risk group (nomogram probability >.5 [50%] or primary tumor grade 2-3 or T2-T4 or cN1-N2, or with lymphovascular invasion), bilateral ILND should be performed (GR B). ILND can be performed at the same time as penectomy, instead of 2-6 weeks later (GR C). SNB based on the anatomic position can be performed, provided the patient is willing to accept the potential false-negative rate of /=2 nodes on one side, contralateral limited ILND with frozen section analysis can be performed, with complete ILND if the frozen section analysis findings are positive (GR B). If clinically suspicious inguinal metastases develop during surveillance, complete ILND should be performed on that side only (GR B), and SNB or limited ILND with frozen section analysis on the contralateral side can be considered (GR C). Endoscopic ILND requires additional study to determine the complication and long-term survival rates (GR C). Pelvic lymph node dissection is recommended if >/=2 proven inguinal metastases, grade 3 tumor in the lymph nodes, extranodal extension (ENE), or large (2-4 cm) inguinal nodes are present, or if the femoral (Cloquet's) node is involved (GR C). Performing ILND before pelvic lymph node dissection is preferable, because pelvic lymph node dissection can be avoided in patients with minimal inguinal metastases, thus avoiding the greater risk of chronic lymphedema (GR B). In patients with numerous or large inguinal metastases, CT or MRI should be performed. If grossly enlarged iliac nodes are present, neoadjuvant chemotherapy should be given and the response assessed before proceeding with pelvic lymph node dissection (GR C). Antibiotic treatment should be started before surgery to minimize the risk of wound infection (GR C). Perioperative low-dose heparin to prevent thromboembolic complications can be used, although it might increase lymph leakage (GR C). The skin incision for ILND should be parallel to the inguinal ligament, and sufficient subcutaneous tissue should be preserved to minimize the risk of skin flap necrosis (GR B). Sartorius muscle transposition to cover the femoral vessels can be used in radical ILND (GR C). Closed suction drainage can be used after ILND to prevent fluid accumulation and wound breakdown (GR B). Early mobilization after ILND is recommended, unless a myocutaneous flap has been used (GR B). Elastic stockings or sequential compression devices are advisable to minimize the risk of lymphedema and thromboembolism (GR C). Radiotherapy to the inguinal areas is not recommended in patients without cytologically or histologically proven metastases nor in those with micrometastases, but it can be considered for bulky metastases as neoadjuvant therapy to surgery (GR B). Adjuvant radiotherapy after complete ILND can be considered in patients with multiple or large inguinal metastases or ENE (GR C). Adjuvant chemotherapy after complete ILND can be used instead of radiotherapy in patients with >/=2 inguinal metastases, large nodes, ENE, or pelvic metastases (GR C). Follow-up should be individualized according to the histopathologic features and the management chosen for the primary tumor and inguinal nodes (GR B).
    • Management of unresectable stage III non-small-cell lung cancer with combined-modality therapy: a review of the current literature and recommendations for treatment.

      Bayman, Neil A; Blackhall, Fiona H; Jain, Pooja; Lee, Lip W; Thatcher, Nick; Faivre-Finn, Corinne; Department of Clinical Oncology, Christie Hospital, Manchester, UK. neil.bayman@christie.nhs.uk (2008-03)
      Lung cancer remains the most common cause of cancer deaths in the United Kingdom, and long-term survival from lung cancer has hardly improved over the past 30 years. The benefit of combined-modality therapy with chemotherapy and radiation therapy in improving survival for patients with inoperable non-small-cell lung cancer (NSCLC) was discovered over 10 years ago. In this comprehensive literature review, we discuss the current status of combined-modality therapy for unresectable stage III NSCLC. The efficacy and toxicity of different chemoradiation therapy regimens are presented. The potential role of novel and targeted therapies and radiation dose escalation is also considered. Finally, recommendations are made for the treatment of unresectable stage III NSCLC.
    • Measurement tools for gastrointestinal symptoms in radiation oncology.

      West, Catharine M L; Davidson, Susan E; Academic Department of Radiation Oncology, The University of Manchester, UK. Catharine.West@manchester.ac.uk (2009-03)
      PURPOSE OF REVIEW: To review the use of measurement tools for reporting gastrointestinal toxicity in radiation oncology to highlight recent findings of potential interest to those involved in the treatment of tumors in the pelvis, assessment of survivorship issues or management of bowel effects. RECENT FINDINGS: Multiple measurement tools are being used in radiation oncology studies involving both clinician and patient-reported outcomes. The increasing availability of accurate data on radiation doses and dose-volumes to normal tissues is enabling identification of critical areas where dose should be reduced to minimize organ damage. SUMMARY: Measurement tools for gastrointestinal symptoms are important to highlight therapeutic benefit for the expanding investigations of treatment intensification approaches and methods for toxicity reduction. The increasing use of the CTCAEv3 scales is a step forward, but further research is required to refine the system and improve its ease of use within routine clinical practice.
    • Metastatic bladder cancer: a review of current management.

      Fletcher, Andrew; Choudhury, Ananya; Alam, Nooreen; Department of Palliative and Supportive Care, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK. (2011)
      Bladder cancer continues to result in substantial morbidity and mortality for affected individuals. Advances in the management of metastatic bladder cancer have been limited. Chemotherapy with platinum-based regimes remains the mainstay of first-line treatment. Studies investigating alternative regimes have offered no survival advantage. Targeted therapies may offer benefit either as single agent or in combination with chemotherapy. Symptoms due to metastatic bladder cancer impact patients' quality of life, and therefore holistic management is vital. Such management includes radiotherapy, bisphosphonates, and the involvement of specialist palliative care services. This review will discuss the current management for metastatic bladder cancer, future potential treatment modalities, and the evidence to support the management strategies.
    • MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer.

      Choudhury, Ananya; Nelson, L D; Teo, M T W; Chilka, S; Bhattarai, S; Johnston, C F; Elliott, F; Lowery, J; Taylor, C F; Churchman, M; et al. (2010-09-15)
      Radical radiotherapy and surgery achieve similar cure rates in muscle-invasive bladder cancer, but the choice of which treatment would be most beneficial cannot currently be predicted for individual patients. The primary aim of this study was to assess whether expression of any of a panel of DNA damage signaling proteins in tumor samples taken before irradiation could be used as a predictive marker of radiotherapy response, or rather was prognostic. Protein expression of MRE11, RAD50, NBS1, ATM, and H2AX was studied by immunohistochemistry in pretreatment tumor specimens from two cohorts of bladder cancer patients (validation cohort prospectively acquired) treated with radical radiotherapy and one cohort of cystectomy patients. In the radiotherapy test cohort (n = 86), low tumor MRE11 expression was associated with worse cancer-specific survival compared with high expression [43.1% versus 68.7% 3-year cause-specific survival (CSS), P = 0.012] by Kaplan-Meier analysis. This was confirmed in the radiotherapy validation cohort (n = 93; 43.0% versus 71.2%, P = 0.020). However, in the cystectomy cohort (n = 88), MRE11 expression was not associated with cancer-specific survival, commensurate with MRE11 being a predictive marker. High MRE11 expression in the combined radiotherapy cohort had a significantly better cancer-specific survival compared with the high-expression cystectomy cohort (69.9% versus 53.8% 3-year CSS, P = 0.021). In this validated immunohistochemistry study, MRE11 protein expression was shown and confirmed as a predictive factor associated with survival following bladder cancer radiotherapy, justifying its inclusion in subsequent trial designs. MRE11 expression may ultimately allow patient selection for radiotherapy or cystectomy, thus improving overall cure rates.
    • Mucosal melanoma of the head and neck: radiotherapy or surgery?

      Douglas, Catriona Mairi; Malik, Tass; Swindell, Ric; Lorigan, Paul C; Slevin, Nicholas J; Homer, Jarrod J; Department of Head and Neck Surgery, Christie Hospital, Manchester, United Kingdom. (2010-08)
      INTRODUCTION: Head and neck mucosal melanoma (MuM) is rare, comprising < 1% of all melanomas in Western Europe. METHODS: A retrospective analysis of case records of patients treated between 1965 and 2001 was carried out. (Survival outcomes were obtained from the case notes and cancer registry.) The median age of the 68 patients was 63 years (range 29-86 years). Thirty-nine percent were male, and 61% were female. (The minimum follow-up time was 15 months.) The two most common primary sites were the sinonasal complex (65%) and oral cavity (19%). Twenty-one percent of patients presented with metastases (nodal or distant). Fifty-five patients were treated with curative intent: 30 patients with primary radiotherapy and 25 patients with surgery +/- postoperative radiotherapy. RESULTS: The overall survival was 22% at 5 years, and the cancer-specific survival was 32% at 5 years. CONCLUSION: MuM has a poor overall prognosis. Poor prognostic indicators are site at presentation and presentation with metastasis. This series is unique in that a significant proportion of patients were given primary radiotherapy as definitive treatment. Surgery may have advantages, particularly for oral cavity MuM. In contrast to previous reports, definitive radiotherapy is worthy of consideration as curative treatment.
    • 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.