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PURPOSE To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM). METHODS In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and KRAS mutation status. RESULTS Four hundred twenty-eight patients from 95 centers in North America, Europe, and Asia were randomly assigned to chemotherapy with or without TARE; this represents the intention-to-treat population and included 215 patients in the TARE plus chemotherapy group and 213 patients in the chemotherapy alone group. The hazard ratio (HR) for PFS was 0.69 (95% CI, 0.54 to 0.88; 1-sided P = .0013), with a median PFS of 8.0 (95% CI, 7.2 to 9.2) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. The HR for hPFS was 0.59 (95% CI, 0.46 to 0.77; 1-sided P < .0001), with a median hPFS of 9.1 (95% CI, 7.8 to 9.7) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. Objective response rates were 34.0% (95% CI, 28.0 to 40.5) and 21.1% (95% CI, 16.2 to 27.1; 1-sided P = .0019) for the TARE and chemotherapy groups, respectively. Median overall survival was 14.0 (95% CI, 11.8 to 15.5) and 14.4 months (95% CI, 12.8 to 16.4; 1-sided P = .7229) with a HR of 1.07 (95% CI, 0.86 to 1.32) for TARE and chemotherapy groups, respectively. Grade 3 adverse events were reported more frequently with TARE (68.4% v 49.3%). Both groups received full chemotherapy dose intensity. CONCLUSION The addition of TARE to systemic therapy for second-line CLM led to longer PFS and hPFS. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.

AIM To evaluate the outcome of patients with bilobar colorectal liver metastases (CRLM) and identify clinico-pathological variables that influenced survival. METHODS Patients with bilobar CRLM were identified from a prospectively maintained hepatobiliary database during the study period (January 2010-June 2014). Collated data included demographics, primary tumour treatment, surgical data, histopathology analysis and clinical outcome. Down-staging therapy included Oxaliplatin- or Irinotecan- based regimens, and Cetuximab was also used in patients that were K-RAS wild-type. Response to neo-adjuvant therapy was assessed at the multi-disciplinary team meeting and considered for surgery if all macroscopic CRLM were resectable with a clear margin while preserving sufficient liver parenchyma. RESULTS Of the 136 patients included, thirty-two (23.5%) patients were considered inoperable and referred for palliative chemotherapy, and thirty-four (25%) patients underwent liver resection. Seventy (51.4%) patients underwent down-staging therapy, of which 37 (52.8%) patients responded sufficiently to undergo liver resection. Patients that failed to respond to down-staging therapy (n = 33, 47.1%) were referred for palliative therapy. There was a significant difference in overall survival between the three groups (surgery vs down-staging therapy vs inoperable disease, P < 0.001). All patients that underwent hepatic resection, including patients that had down-staging therapy, had a significantly better overall survival compared to patients that were inoperable (P < 0.001). On univariate analysis, only resection margin significantly influenced disease-free survival (P = 0.017). On multi-variate analysis, R0 resection (P = 0.030) and female (P = 0.036) gender significantly influenced overall survival. CONCLUSION Patients undergoing liver resection with bilobar CRLM have a significantly better survival outcome. R0 resection is associated with improved disease-free and overall survival in this patient group.

At the recent Pump Industry Awards, Jamie Mills won the Engineer of the Year award, sponsored by World Pumps magazine. Here, Jamie talks about his career in the industry, his work with a major water technology provider and considers his future and that of the pump industry.

3507 Background: The FOXFIRE, SIRFLOX and FOXFIRE-Global (FF-SF-FFG) randomized studies evaluated the efficacy of combining first-line chemotherapy for metastatic colorectal cancer (mCRC) with selective internal radiotherapy (SIRT) using yttrium-90 resin microspheres in patients with liver metastases. The studies were designed for prospective, combined analysis of overall survival (OS). Methods: FF-SF-FFG randomized (1:1) chemotherapy-naïve mCRC patients (performance status 0/1) with liver metastases not suitable for curative resection/ablation. Arm A was oxaliplatin-based chemotherapy (mFOLFOX6/ OxMdG) ± investigator-chosen biologically targeted agent. Arm B was the same systemic therapy (oxaliplatin dose modification) + single treatment SIRT with cycle 1/2 of chemotherapy. Primary tumor in situ and/or limited extra-hepatic metastases were permitted. Minimum sample size was 1075 patients (HR 0.8, 80% power, two-sided 5% significance). Secondary outcomes included PFS, liver-specific PFS and response rate. Apart from safety, outcomes were analysed on intention-to-treat population using meta-analytic methods of pooled individual patient data. Results: Between 2006 and 2014, 1103 patients were randomized in 14 countries. Median age was 63 years (range 23-89); median follow-up 43.3 months. There were 844 deaths. There was no difference in OS (HR 1.04; 95% CI 0.90-1.19, p= 0.609) or PFS (HR 0.90, CI 0.79-1.02, p= 0.108) between Arms. Objective response rate ( p= 0.001) and liver-specific progression (HR 0.51, CI 0.43-0.62, p< 0.001) were significantly more favorable in Arm B. Patients in Arm B had higher risk of non-liver progression as first event (HR 1.98, CI 1.53-2.58, p< 0.001). Grade 3-5 adverse events were more common in Arm B (74.0%) than A (66.5%), p= 0.009. In health status questionnaires, EQ-5D utility scores were not significantly different between Arms at 6, 12 or 24 months. Conclusion: Despite higher response rates and improved liver-specific PFS, the addition of SIRT to first-line oxaliplatin-fluorouracil chemotherapy for patients with liver-only and liver-dominant mCRC did not improve OS or PFS. Clinical trial information: 83867919.

A 62-year-old woman received six cycles of docetaxel chemotherapy during a six-month period for recurrent metastatic breast cancer. She had completed treatment four weeks before this photograph was taken. Six evenly spaced, transverse lines were noted on all her fingernails. Beau's lines are transverse depressions in the nail plate caused by temporary cessation of cell division in the proximal nail matrix. The condition may be caused by local disease of the nail fold or a systemic insult, such as an illness or the administration of a drug.

Contrast thresholds for the detection of flicker and the detection of pattern were measured for nasal and temporal retinae of each eye separately. While confirming that these two types of thresholds can differ, depending on spatial frequency, the results provide no support for hemiretinal or hemispheric asymmetries in the distribution of the putative pattern and movement channels.