• Non-standard radical treatment of skin cancer.

      McPartlin, Andrew J; Slevin, Nicholas J; The Christie Hospital NHS Foundation Trust, Manchester (2011-09)
    • 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
    • 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.
    • Psoas abscess: an unusual presentation of a metastatic breast cancer after 25 years.

      Satpathy, Anjana; Burt, Paul A; Guy, Andrew J; Department of General Surgery, Leighton Hospital, Crewe, UK. anjana_satpathy@yahoo.co.uk (2009-04-01)
    • Radiotherapy for the treatment of longstanding head and neck hemangioma.

      Douglas, Catriona Mairi; Ho, Kean F; Homer, Jarrod J; Slevin, Nicholas J; Department of Otolaryngology-Head and Neck Surgery, Christie Hospital, Manchester, UK. Catriona.douglas@christie.nhs.uk (2009-08)
    • Randomised phase II trial of 4 dose levels of single agent docetaxel in performance status (PS) 2 patients with advanced non-small cell lung cancer (NSCLC): DOC PS2 trial. Manchester lung cancer group.

      Califano, Raffaele; Griffiths, Richard W; Lorigan, Paul C; Ashcroft, Linda; Taylor, Paul; Burt, Paul A; Lee, Lip W; Chittalia, Abbas; Harris, Maggie A; Faivre-Finn, Corinne; et al. (2011-09)
      The role of chemotherapy for advanced NSCLC patients and ECOG PS2 remains controversial. We evaluated 4 doses of 3-weekly docetaxel to identify a less toxic, clinically effective dose.
    • Rectal motion can reduce CTV coverage and increase rectal dose during prostate radiotherapy: A daily cone-beam CT study.

      Sripadam, Raj; Stratford, Julia; Henry, Ann M; Jackson, Andrew; Moore, Christopher J; Price, Patricia M; Clatterbridge Centre for Oncology, Bebington, Wirral, UK. (2009-03)
      BACKGROUND AND PURPOSE: Daily on-treatment verification cone-beam CT (CBCT) was used to study the effect of rectal motion on clinical target volume (CTV) coverage during prostate radiotherapy. MATERIAL AND METHODS: CBCT scans were acquired from 15 patients immediately after daily treatment. From these images, the rectum was contoured allowing the analysis of rectal volume cross-sectional area (CSA) and the determination of rectal dose. Rectal wall motion was quantified as a surrogate measure of prostate displacement and CTV coverage was subjectively assessed. RESULTS: Rectal volume decreased over the treatment course in 13 patients (P<0.001). Rectal wall regions corresponding to the prostate base displayed the greatest motion; larger displacements were seen in patients with larger rectal planning volumes. CTV coverage was inadequate, at the prostate base only, in 38% of the fractions delivered to 4/7 patients with a large rectum at planning (>100 cm(3)). In patients with small rectum at planning (<50 cm(3)) up to 25% more rectal volume than predicted was included in the high-dose region. CONCLUSIONS: Rectal motion during treatment in prostate cancer patients has implications for CTV coverage and rectal dose. Measures to ensure consistency in daily rectal volume or image-guided strategies should be considered.
    • Report on the early efficacy and tolerability of I(125) permanent prostate brachytherapy from a UK multi-institutional database.

      Mitchell, Darren M; Mandall, Paula; Bottomley, David; Hoskin, Peter J; Logue, John P; Ash, D; Ostler, P; Elliott, Tony; Henry, Ann M; Wylie, James P; et al. (2008-12)
      AIMS: To report the results of I(125) prostate brachytherapy from a central, prospectively collected database of three UK institutions. MATERIALS AND METHODS: All patients treated with I(125) permanent prostate brachytherapy at the Christie Hospital, Manchester (CHM), Cookridge Hospital, Leeds (CKL) and Mount Vernon Hospital, Northwood, London (MVL) since 2003 have been prospectively registered on a detailed central database. Patient, tumour, pre- and post-implant dosimetry data have been recorded. Urinary toxicity as assessed by the International Prostate Symptom Score, catheterisation and urinary stricture rates after implant have been documented and biochemical failure determined, using both the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and the Phoenix (nadir + 2 ng/ml) definition. RESULTS: In total, 1535 patients were registered on the database between January 2003 and October 2006, including 432 from CHM, 926 from CKL and 177 from MVL, with a median follow-up of 21 months (range 1-56). Patient and tumour characteristics were similar at all centres. Pre-implant dose indices were comparable between centres, except for the V150, with median values of 51.9, 64.3 and 69.8% at CHM, CKL and MVL, respectively. Median post-implant dose parameters were lower than pre-planned constraints by up to 33.0% at each centre for all values, except at CKL where the V200 was 23.9% higher. The International Prostate Symptom Score increased from a median of 5 at baseline to 18, 6 weeks after implant, but was not significantly different to baseline values by 12 months. Nine per cent of men required catheterisation after implant for a median duration of 53 days, but urinary stricture rates remained low at 1%. Neoadjuvant hormonal manipulation was used in 228 men (15%) for downsizing and 159 (10%) for intermediate/high-risk disease. Collated biochemical failure rates were low at this point of follow-up, with actuarial 2-year ASTRO and Phoenix biochemical failure-free survival rates of 94.4 and 94.5%, respectively, consistent with other large single centre reports. When post-implant dosimetric factors were assessed for a relationship to biochemical failure, no indices consistently predicted for improved ASTRO and Phoenix biochemical failure-free survival rates. CONCLUSIONS: This ongoing collaboration shows that with limited infrastructure (a single industry-sponsored data manager), a large multi-institutional database estimated to represent one-third of implants carried out in the UK during this time can be developed. Patient selection was similar across all centres and adhered to published guidelines. Early biochemical and toxicity outcomes confirm the efficacy and tolerability of I(125) prostate brachytherapy in a large cohort of patients. A further analysis is planned.
    • Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomised clinical trial.

      Le Péchoux, Cécile; Dunant, Ariane; Senan, Suresh; Wolfson, Aaron; Quoix, Elisabeth; Faivre-Finn, Corinne; Ciuleanu, Tudor; Arriagada, Rodrigo; Jones, Richard C; Wanders, Rinus; et al. (2009-05)
      BACKGROUND: The optimum dose of prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (SCLC) is unknown. A meta-analysis suggested that the incidence of brain metastases might be reduced with higher PCI doses. This randomised clinical trial compared the effect of standard versus higher PCI doses on the incidence of brain metastases. METHODS: Between September, 1999, and December, 2005, 720 patients with limited-stage SCLC in complete remission after chemotherapy and thoracic radiotherapy from 157 centres in 22 countries were randomly assigned to a standard (n=360, 25 Gy in 10 daily fractions of 2.5 Gy) or higher PCI total dose (n=360, 36 Gy) delivered using either conventional (18 daily fractions of 2 Gy) or accelerated hyperfractionated (24 fractions in 16 days with two daily sessions of 1.5 Gy separated by a minimum interval of 6 h) radiotherapy. All of the treatment schedules excluded weekends. Randomisation was stratified according to medical centre, age (60 years), and interval between the start of induction treatment and the date of randomisation (180 days). Eligible patients were randomised blindly by the data centre of the Institut Gustave Roussy (PCI99-01 and IFCT) using minimisation, and by the data centres of EORTC (EORTC ROG and LG) and RTOG (for CALGB, ECOG, RTOG, and SWOG), both using block stratification. The primary endpoint was the incidence of brain metastases at 2 years. Analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov number NCT00005062. FINDINGS: Five patients in the standard-dose group and four in the higher-dose group did not receive PCI; nonetheless, all randomised patients were included in the effectiveness anlysis. After a median follow-up of 39 months (range 0-89 months), 145 patients had brain metastases; 82 in the standard-dose group and 63 in the higher-dose group. There was no significant difference in the 2-year incidence of brain metastases between the standard PCI dose group and the higher-dose group, at 29% (95% CI 24-35) and 23% (18-29), respectively (hazard ratio [HR] 0.80 [95% CI 0.57-1.11], p=0.18). 226 patients in the standard-dose group and 252 in the higher-dose group died; 2-year overall survival was 42% (95% CI 37-48) in the standard-dose group and 37% (32-42) in the higher-dose group (HR 1.20 [1.00-1.44]; p=0.05). The lower overall survival in the higher-dose group is probably due to increased cancer-related mortality: 189 patients in the standard group versus 218 in the higher-dose group died of progressive disease. Five serious adverse events occurred in the standard-dose group versus zero in the higher-dose group. The most common acute toxic events were fatigue (106 [30%] patients in the standard-dose group vs 121 [34%] in the higher-dose group), headache (85 [24%] vs 99 [28%]), and nausea or vomiting (80 [23%] vs 101 [28%]). INTERPRETATION: No significant reduction in the total incidence of brain metastases was observed after higher-dose PCI, but there was a significant increase in mortality. PCI at 25 Gy should remain the standard of care in limited-stage SCLC. FUNDING: Institut Gustave-Roussy, Association pour la Recherche sur le Cancer (2001), Programme Hospitalier de Recherche Clinique (2007). The European Organisation for Research and Treatment of Cancer (EORTC) contribution to this trial was supported by grants 5U10 CA11488-30 through 5U10 CA011488-38 from the US National Cancer Institute.
    • Symptom experience in patients with primary brain tumours: a longitudinal exploratory study.

      Molassiotis, Alexander; Wilson, Barbara; Brunton, Lisa; Chaudhary, Haseeb; Gattamaneni, Rao; McBain, Catherine A; University of Manchester, School of Nursing, University Place, Manchester M13 9PL, UK. alex.molassiotis@manchester.ac.uk (2010-12)
      This study was undertaken to further understand the symptom experience and the impact of symptoms in daily life in people treated for brain tumours.
    • Synchronous chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck using capecitabine: a single-centre, open-label, single-group phase II study.

      Jegannathen, Apurna; Mais, Kathleen L; Sykes, Andrew J; Lee, Lip W; Yap, Beng K; Birzgalis, Andrew R; Homer, Jarrod J; Ryder, W David J; Slevin, Nicholas J; Department of Clinical Oncology, Christie NHS Foundation Trust, Manchester, UK. (2011-03)
      To evaluate the efficacy of concurrent oral capecitabine with accelerated hypofractionated radical radiotherapy in locally advanced squamous cell carcinoma of the head and neck (SCCHN).
    • UGT1A1*28 genotype predicts gastrointestinal toxicity in patients treated with intermediate-dose irinotecan.

      Ferraldeschi, Roberta; Minchell, Laura J; Roberts, Stephen A; Tobi, Simon; Hadfield, Kristen D; Blackhall, Fiona H; Mullamitha, Saifee A; Wilson, Gregory; Valle, Juan W; Saunders, Mark P; et al. (2009-05)
      AIMS: Variants in UGT1A1 have previously been associated with toxicity from irinotecan chemotherapy. We conducted a pragmatic prospective cohort study to establish the relevance of UGT1A1 variants in the prediction of severe diarrhea and neutropenia in patients with colorectal cancer receiving irinotecan in a routine clinical setting. MATERIALS & METHODS: Genotyping of UGT1A1*28 and c.-3156G>A was undertaken in an unselected, prospective cohort of 96 individuals treated with irinotecan at a single major UK oncology centre. Data on cytotoxic drugs received, and toxicity for all irinotecan treatment cycles were collected from case notes. Over 95% (92/96) of patients received an intermediate dose of irinotecan (180 mg/m(2), twice weekly). Irinotecan was given in combination with other cytotoxic drugs in 93/96 subjects and Grade 3 or 4 toxicity occurred in 23% of subjects. RESULTS: No association was found between UGT1A1*28 or c.-3156G>A and neutropenia. However, individuals carrying two copies of UGT1A1*28 (p = 0.04; OR: 14; 95% CI: 1.1-185) or c.-3156G>A (p = 0.03) had a significantly increased risk of diarrhea over all cycles. CONCLUSION: Our findings indicate that UGT1A1 genotyping is not a good predictor of hematological toxicity in patients treated with intermediate irinotecan doses. However, it may be useful in the identification of patients at risk of severe diarrhea.
    • Use of G-CSF during concurrent chemotherapy and thoracic radiotherapy in patients with limited-stage small-cell lung cancer safety data from a phase II trial.

      Sheikh, Hamid Y; Colaco, Rovel J; Lorigan, Paul C; Blackhall, Fiona H; Califano, Raffaele; Ashcroft, Linda; Taylor, Paul; Thatcher, Nick; Faivre-Finn, Corinne; Dept of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK. (2011-10)
      There is paucity of data in the literature regarding the safety of combining granulocyte colony stimulating factor (G-CSF) during chemo-radiotherapy (CTRT) in lung cancer patients. The ASCO 2006 recommendations advise against use of CSFs during concomitant mediastinal CTRT. The only randomised study evaluating CSFs in this context showed significant increase in grade 3/4 thrombocytopenia and an excess of pulmonary toxic deaths. In the context of a phase II trial, 38 patients with limited-stage small cell lung cancer were randomised to receive once-daily (66 Gy in 33 fractions) or twice-daily (45 Gy in 30 fractions) radiotherapy. Radiotherapy (RT) was given concurrently with cisplatin and etoposide. G-CSF was given as primary or secondary prophylaxis or as a therapeutic measure during an episode of febrile neutropenia according to local protocols. Common terminology criteria for adverse events (CTCAE) v3.0 was used to record toxicity. Thirteen (34%) of 38 patients received G-CSF concurrently with RT. With a median follow-up of 16.9 months, there were no treatment related deaths reported. Seven (54%) patients experienced grade 3/4 thrombocytopenia and 5 (38%) experienced grade 3/4 anaemia. Thirty-one percent required platelet transfusions. No episodes of bleeding were observed. There were no cases of grade 3/4 acute pneumonitis. These data suggests that with modern three-dimensional (3D) conformal RT, G-CSF administration concurrently with CTRT does not result in the increase risk of pulmonary toxicity, but does increase the risk of thrombocytopenia. Whether the risks of thrombocytopenia are outweighed by the outcome of timely early concurrent CTRT is being evaluated prospectively in the ongoing phase III CONVERT trial (NCT00433563) in which G-CSF is permitted during thoracic irradiation.
    • Use of multiple biological markers in radiotherapy-treated head and neck cancer.

      Silva, Priyamal; Slevin, Nicholas J; Sloan, Philip; Valentine, Helen R; Ryder, W David J; Price, Patricia M; West, Catharine M L; Homer, Jarrod J; School of Cancer & Enabling Sciences, The University of Manchester, Manchester, UK. (2010-06)
      OBJECTIVE: Management of patients with head and neck squamous cell carcinoma is often based on clinical parameters, with little appreciation of the underlying tumour biology. Single biological marker studies fail to acknowledge the complexity of these tumours. Our aim was to define a profile of biological markers associated with outcome. DESIGN: This retrospective study involved consecutive patients with oropharyngeal squamous cell carcinoma treated with primary radiotherapy between 1996 and 2001. Pre-treatment biopsies were used to study the immunohistochemical expression of nine biological markers. Markers were chosen to reflect biologically relevant pathways. RESULTS: Following analysis of nine markers, a profile of two markers was derived (carbonic anhydrase 9 and major vault protein), the co-expression of which conferred a significantly poor probability of locoregional control. The prognostic effect of these biomarkers in combination was greater than their effect individually. CONCLUSION: Biomarker profiles can be established which highlight large differences in locoregional control. Identifying tumours that express both carbonic anhydrase 9 and major vault protein may facilitate patient selection for more aggressive treatment.