Can we accurately report PTEN status in advanced colorectal cancer?

BACKGROUND: Loss of phosphatase and tensin homologue (PTEN) function evaluated by loss of PTEN protein expression on immunohistochemistry (IHC) has been reported as both prognostic in metastatic colorectal cancer and predictive of response to anti-EGFR monoclonal antibodies although results remain uncertain. Difficulties in the methodological assessment of PTEN are likely to be a major contributor to recent conflicting results. METHODS: We assessed loss of PTEN function in 51 colorectal cancer specimens using Taqman® copy number variation (CNV) and IHC. Two blinded pathologists performed independent IHC assessment on each specimen and inter-observer variability of IHC assessment and concordance of IHC versus Taqman® CNV was assessed. RESULTS: Concordance between pathologists (PTEN loss vs no loss) on IHC assessment was 37/51 (73%). In specimens with concordant IHC assessment, concordance between IHC and Taqman® copy number in PTEN loss assessment was 25/37 (68%). CONCLUSION: Assessment PTEN loss in colorectal cancer is limited by the inter-observer variability of IHC, and discordance of CNV with loss of protein expression. An understanding of the genetic mechanisms of PTEN loss and implementation of improved and standardized methodologies of PTEN assessment are required to clarify the role of PTEN as a biomarker in colorectal cancer

Dual αV-integrin and neuropilin-1 targeting peptide CEND-1 plus nab-paclitaxel and gemcitabine for the treatment of metastatic pancreatic ductal adenocarcinoma : a first-in-human, open-label, multicentre, phase 1 study

Peer reviewe

A descriptive study of persistent oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer

Background\ud \ud Prolonged neurotoxicity after systemic chemotherapy has the potential to impact on quality of life. We explored the frequency of persistent peripheral neuropathy in patients who received oxaliplatin for colorectal cancer at two local centres.\ud Patients and methods\ud \ud Questionnaires were sent to patients who completed treatment with oxaliplatin for colorectal cancer at least 20 months prior to entering the study. Neuropathy questions were adapted from the FACT/GOG-Ntx (V.4) questionnaire.\ud \ud Results\ud \ud Of the 56 eligible patients, 27 returned the questionnaire. Twenty-five patients (93 %) experienced neuropathic symptoms during their treatment; 11 had grade-2, and two had grade-3 symptoms. At the time of completing the questionnaire, 17 patients (63.0 %; 95%CI 43.9–79.4 %) were still symptomatic with 12 patients (44.4 %; 95%CI 26.8–63.3) having grade-2 or grade-3 symptoms and three patients (11.1 %; 95%CI 2.9–27.3) having grade-3 neuropathic symptoms. Participants who received more than 900 mg/m^2 oxaliplatin had a significantly higher risk of persistent grade-2 or grade-3 neuropathy (p = 0.031, RR = 8.3 95%CI = 1.2–57.4). There was a trend toward increased risk of persistent neuropathy of any grade among participants with a history of regular alcohol use (p = 0.051; RR = 1.7 95%CI 1.0–2.8).\ud \ud Conclusion\ud \ud Persistent oxaliplatin-induced neuropathy is not as uncommon as previously suggested, and the rate of grade-2 and grade-3 symptoms could be considerably higher than previous reports