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The VEGF-A monoclonal antibody bevacizumab is currently recommended for first-line treatment of all metastatic colorectal cancer (mCRC) patients. Cost-benefit ratio and side-effects however necessitate patient selection. A large retrospective yet nonrandomized study showed that patients with loss of chromosome 18q11.2-q12.1 in the tumor and treated with bevacizumab have 3 months improved median progression-free (PFS) and overall survival (OS) benefit compared to patients without this loss and/or treatment modality. Implementation for loss of chromosome 18q11.2-q12.1 as a marker in clinical practice mandates evidence in a randomized controlled trial for bevacizumab. Of the trials with randomization of chemotherapy vs chemotherapy with bevacizumab, the AGITG-MAX trial was the only one with tumor materials available. Chromosome 18q11.2-q12.1 copy number status was measured for 256 AGITG-MAX trial patients and correlated with PFS according to a predefined analysis plan with marker-treatment interaction as the primary end-point. Chromosome 18q11.2-q12.1 losses were detected in 71% of patients (181/256) characteristic for mCRC. Consistent with the nonrandomized study, significant PFS benefit of bevacizumab was observed in patients with chromosome 18q11.2-q12.1 loss (P =.009), and not in patients without 18q loss (P =.67). Although significance for marker-treatment interaction was not reached (Pinteraction =.28), hazard ratio and 95% confidence interval of this randomized cohort (HRinteraction = 0.72; 95% CI = 0.39-1.32) shows striking overlap with the nonrandomized study cohorts (HRinteraction = 0.41; 95% CI = 0.32-0.8) supported by a nonsignificant Cochrane χ2 test (P =.11) for heterogeneity. We conclude that post hoc analysis of the AGITG-MAX RCT provides supportive evidence for chromosome 18q11.2-q12.1 as a predictive marker for bevacizumab in mCRC patients.

Epigenetics; Tumour-suppressor proteins Epigenética; Proteínas supresoras de tumores Epigenètica; Proteïnes supresores de tumors Colorectal cancers (CRCs) often display histological features indicative of aberrant differentiation but the molecular underpinnings of this trait and whether it directly drives disease progression is unclear. Here, we identify co-ordinate epigenetic inactivation of two epithelial-specific transcription factors, EHF and CDX1, as a mechanism driving differentiation loss in CRCs. Re-expression of EHF and CDX1 in poorly-differentiated CRC cells induced extensive chromatin remodelling, transcriptional re-programming, and differentiation along the enterocytic lineage, leading to reduced growth and metastasis. Strikingly, EHF and CDX1 were also able to reprogramme non-colonic epithelial cells to express colonic differentiation markers. By contrast, inactivation of EHF and CDX1 in well-differentiated CRC cells triggered tumour de-differentiation. Mechanistically, we demonstrate that EHF physically interacts with CDX1 via its PNT domain, and that these transcription factors co-operatively drive transcription of the colonic differentiation marker, VIL1. Compound genetic deletion of Ehf and Cdx1 in the mouse colon disrupted normal colonic differentiation and significantly enhanced colorectal tumour progression. These findings thus reveal a novel mechanism driving epithelial de-differentiation and tumour progression in CRC. This project was supported by NHMRC project grant (1107831), a Cancer Council Victoria Grant (1164674) and the Operational Infrastructure Support Programme, Victorian Government, Australia. JMM was supported by a NHMRC Senior Research Fellowship (1046092). IYL was supported by F J Fletcher Research Scholarship and Randal and Louisa Alcock Scholarship from the University of Melbourne. LJJ was supported by La Trobe University Australian Postgraduate Awards. IN was supported by La Trobe University Postgraduate Research Scholarship. JWTT was supported by the University of Melbourne Australian Postgraduate Awards. OMS is a National Health and Medical Research Council (NHMRC) Senior Research Fellow (APP1136119). Open Access funding enabled and organized by CAUL and its Member Institutions.

To compare clinical tear film break-up time measurements obtained non-invasively, with those measured following minimal and conventional volumes of fluorescein instillation.Forty-one subjects (20 male, 21 female, mean±SD age 34±11years), with or without dry eye, participated in a prospective cross-over study. Tear film break-up time was measured by the Tearscope Plus™ with fine grid insert. Measurements were made in triplicate, with no fluorescein instillation (NIBUT), then following application of a minimal volume of 1μl fluorescein from the Dry Eye Test™ (mTBUT), and finally with 15-30μl of fluid instilled via a conventional fluorescein strip (TBUT). A fifteen-minute interval between each set of measurements minimised the risk of residual contamination effects.All three techniques displayed statistically significant pairwise correlation (all p0.001). TBUT values were significantly shorter than both NIBUT (geometric mean 8.6s versus 10.9s, p=0.03) and mTBUT (geometric mean 8.6s versus 10.6s, p=0.03), and demonstrated narrower spread (both p0.05). No significant differences were detected between NIBUT and mTBUT (all p0.05).Tear film break-up time values measured with conventional fluorescein instillation were shortened, while minimal fluorescein instillation and non-invasive methods produced comparable readings. This suggests that minimising instilled volumes can reduce the impact of fluorescein on clinical measurements of tear film stability.

Problem: Townsville Cancer Centre provides video-consultation (VC) services to patients in rural/remote regions of North Queensland in order to improve access to specialist cancer care. The experience and responses of indigenous patients using this service have not been studied. Our objective is to assess the level of satisfaction and the responses of Indigenous patients, their families and health workers (HWs) to VC and such teleoncology service. Design: Descriptive study, using semistructured interviews. Setting: Tertiary referral centre (Townsville Cancer Centre) and various rural and remote towns in Queensland. Key measures for improvement: Satisfaction levels of Indigenous patients, their family members and Indigenous HWs with various aspects of the teleoncology service. Lessons learnt: Our evaluation suggests that teleoncology is an acceptable model of care for Indigenous patients, with high levels of satisfaction expressed from patients, families and HWs. Health professionals involved with providing this service need to be adaptive to the needs of individual patients and local communities in order to provide culturally appropriate care. Formal skills training for staff, effective communication between specialist and local HWs, and informed consent procedures are essential to maintain safety of practices. Strategies for change are: • Mandatory informed consent procedure for all patients offered with VC. • Formalised competency training for staff in skills essential to maintain safe practices in teleoncology. • Clear clinical documentation to facilitate improved communication in patient management between medical staff at main centre and distant sites. • Further efforts in promotion, education and support for staff to participate in telemedicine.

AIMS: In this retrospective analysis, we describe the efficacy and tolerability of weekly cisplatin 40 mg/m(2) used in concurrent chemoradiation of head and neck cancer at the Townsville Cancer Centre. METHODS: Review of medical records of patients who received radical chemoradiotherapy for head and neck cancer at Townsville Cancer Centre from 2003 to 2009. RESULTS: In all 102 patients were analysed, 62 of whom had definitive chemoradiation and the remainder adjuvant chemoradiotherapy. Median follow up was 20.1 months (range 5-86 months). Overall 68.6% of patients received 5 weeks or more of planned chemotherapy. Radiotherapy interruptions occurred in four (6.4%) patients. The rate of grade 3-4 adverse events was 51% including neutropenia (18.6%), mucositis (21.8%) and dysphagia (12.9%) and 30.7% of patients needed hospital admission to manage toxicities. For definitive and adjuvant groups, estimated 3-year survival was 64.5 and 71.5%, respectively, and estimated 3-year disease-specific survival rates were 70.3 and 81.6%, respectively. The 3-year overall survival for patients who received five or more cycles of chemotherapy was 75.2%, compared to 52.6% for those receiving fewer than five cycles (P = 0.018). CONCLUSION: Despite this is being a small retrospective study, survival figures and toxicity profiles of low dose weekly cisplatin are comparable to historical controls using high-dose regimens, hence justifying our approach. In addition, radiotherapy interruptions are minimized and cisplatin is easy to administer in outpatient settings. Future three-arm studies could include this regimen as the basis of treatment combined with targeted therapies.

Townsville Cancer Centre provides video-consultation (VC) services to patients in rural/remote regions of North Queensland in order to improve access to specialist cancer care. The experience and responses of indigenous patients using this service have not been studied. Our objective is to assess the level of satisfaction and the responses of Indigenous patients, their families and health workers (HWs) to VC and such teleoncology service.Descriptive study, using semistructured interviews.Tertiary referral centre (Townsville Cancer Centre) and various rural and remote towns in Queensland.Satisfaction levels of Indigenous patients, their family members and Indigenous HWs with various aspects of the teleoncology service.Our evaluation suggests that teleoncology is an acceptable model of care for Indigenous patients, with high levels of satisfaction expressed from patients, families and HWs. Health professionals involved with providing this service need to be adaptive to the needs of individual patients and local communities in order to provide culturally appropriate care. Formal skills training for staff, effective communication between specialist and local HWs, and informed consent procedures are essential to maintain safety of practices. Strategies for change are: • Mandatory informed consent procedure for all patients offered with VC. • Formalised competency training for staff in skills essential to maintain safe practices in teleoncology. • Clear clinical documentation to facilitate improved communication in patient management between medical staff at main centre and distant sites. • Further efforts in promotion, education and support for staff to participate in telemedicine.