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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.

The phase III MAX clinical trial randomised patients with metastatic colorectal cancer (mCRC) to receive first-line capecitabine chemotherapy alone or in combination with the anti-VEGF-A antibody bevacizumab (± mitomycin C). We utilised this cohort to examine whether single nucleotide polymorphisms (SNPs) in VEGF-A, VEGFR1, and VEGFR2 are predictive of efficacy outcomes with bevacizumab or the development of hypertension. Genomic DNA extracted from archival FFPE tissue for 325 patients (69% of the MAX trial population) was used to genotype 16 candidate SNPs in VEGF-A, VEGFR1, and VEGFR2, which were analysed for associations with efficacy outcomes and hypertension. The VEGF-A rs25648 ‘CC’ genotype was prognostic for improved PFS (HR 0.65, 95% CI 0.49 to 0.85; P = 0.002) and OS (HR 0.70, 95% CI 0.52 to 0.94; P = 0.019). The VEGF-A rs699947 ‘AA’ genotype was prognostic for shorter PFS (HR 1.32, 95% CI 1.002 to 1.74; P = 0.048). None of the analysed SNPs were predictive of bevacizumab efficacy outcomes. VEGFR2 rs11133360 ‘TT’ was associated with a lower risk of grade ≥ 3 hypertension (P = 0.028). SNPs in VEGF-A, VEGFR1 and VEGFR2 did not predict bevacizumab benefit. However, VEGF-A rs25648 and rs699947 were identified as novel prognostic biomarkers and VEGFR2 rs11133360 was associated with less grade ≥ 3 hypertension.

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.

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.