No abstract

398 Background: There have been conflicting results about whether KRAS mutation influences outcome in patients (pts) with colorectal cancer. In pts who underwent liver resection, Karagkounis reported a worse recurrence and survival in KRAS mutated (MUT) patients (ASCO 2012, abs 3616). Methods: In 105 pts who underwent liver resection and received adjuvant (adj) hepatic arterial infusion and systemic chemotherapy and in whom KRAS data was available, we evaluated recurrence patterns and survival. Correlation between KRAS and clinical factors such as prior chemotherapy, post operative CEA, clinical risk score, and stage at diagnosis was evaluated using Fisher’s exact test and the Wilcoxon rank sum test. Kaplan-Meier methods were used to estimate median overall recurrence free survival (RFS) and overall survival (OS) at 4 years. Log-rank test was used to determine whether survival functions differed by KRAS mutation status. Cumulative incidence function was used to estimate the probability of time from adj therapy to bone, brain, lung and liver metastases separately. Results: Of 105 patients, 76 were KRAS wildtype (WT), and 29 were KRAS MUT (26-G12 and 3-G13). The median RFS was 26 months for KRAS WT pts and 15 months for KRAS MUT pts (p=0.08). OS at 4 years was 88% [95% CI: 78%-94%] for KRAS WT and 78% [95% CI: 57%-90%] for KRAS MUT pts (p= 0.15). Cumulative incidence of developing bone, brain, lung, and liver metastases by 2 years is presented in the Table. The cumulative incidence of bone and brain metastases at 2 years was 0% and 0% in KRAS WT pts versus 16.4% [95% CI: 1.1%-31.7%] and 4.7% [95% CI: 0%-14.1%] in KRAS MUT pts (Table). There was no association between clinical factors and KRAS status. Conclusions: KRAS MUT pts appeared to have worse OS and RFS, although we were unable to show a significant difference between KRAS WT and MUT for OS and RFS. In addition, cumulative incidence of bone and brain metastases at 2 years appeared to be higher for KRAS MUT pts as compared to WT pts. Results are based on small sample size and further investigation is needed. [Table: see text]

Background The validity of KRAS mutation as a predictor of recurrence free survival (RFS) or overall survival (OS) is unclear. This study investigated whether KRAS mutation decreases RFS or OS in patients with colorectal cancer who underwent liver resection. Methods Patients with resected colorectal liver metastases who were treated with adjuvant hepatic arterial infusion (HAI) plus systemic therapy and in whom KRAS data was available were evaluated. Correlation between KRAS and clinical factors was evaluated using Fisher's exact test. Kaplan-Meier methods were used to estimate median overall RFS and OS. Results 169 patients were evaluated: 118 KRAS wild type (WT) and 51 mutated (MUT). Three year RFS was 46% for KRAS WT [95%CI: 35-56%], and 30% [95%CI: 16-44%] for MUT patients (p=0.005). Three year OS was 95% [87%-98%] and 81% [62%-95%] for KRAS WT and MUT patients, respectively (p=0.07). By multivariate analysis, KRAS remained a significant predictor of RFS (HR: 1.9). Cumulative recurrence by 3 years in sites showed: 2% versus 13.4% for bone metastases (p=<0.01), 2% versus 14.5% for brain (p=0.05), 33.2% versus 58% for lung (p=<0.01), and 30 versus 47% for liver (p=0.10) in KRAS WT versus MUT patients, respectively. Conclusions In patients with resected colorectal liver metastases treated with adjuvant HAI plus systemic therapy, patients with KRAS mutation had a significantly worse 3 year RFS of 46% versus 30% (p=0.005) for KRAS WT vs MUT, respectively. Cumulative incidence of bone, brain, and lung metastases was significantly higher for KRAS MUT patients as compared to WT patients.

Patients with anti-GBM disease with normal renal function are not uncommon, and often have a good prognosis. There is less renal damage, possibly because of lower levels of circulating anti-GBM antibodies and less glomerular complement deposition.

Glioblastoma (GBM) is the most common and aggressive intraparenchymal primary brain tumor in adults. Contemporary multimodality therapy for newly diagnosed patients, consisting of maximal surgical resection, concomitant radiation plus temozolomide (TMZ) followed by adjuvant TMZ 1 has extended the median survival to 15 months, though only 10-26.5% of patients survive longer than two years.2 Treatment is challenging because of the notoriously unpredictable chemosensitivity of GBM which is likely linked to the genetic aberrations underlying its pathogenesis. Molecular biomarkers arising from these aberrations continue to be identified, and have been shown to have predictive and prognostic potential in GBM. In a post facto analysis of the landmark EORTC/NCIC study of adjuvant chemoradiation (CRT) with TMZ, it was suggested that methylation of the O 6 -methylguanine DNA methyltransferase ABSTRACT: Aim: To review the impact of molecular biomarkers on response to therapy and survival in patients with primary glioblastoma (GBM). Materials & Methods: Tissue specimens were analyzed for p53 mutations, EGFR amplification, loss of PTEN and p16, and O 6 -methylguanine DNA methyltransferase (MGMT) promoter methylation. Demographic and clinical data were gathered from medical records. Results: Clinical and pathological data of 125 patients were collected and analysed. MGMT promoter methylation was associated with improved median overall survival (OS) (61 vs. 42 weeks, p = 0.01) and was an important prognosticator independent of age at diagnosis, extent of resection and post-operative ECOG performance status (HR 2.04, 95% CI 1.11-3.75). Among patients with MGMT promoter methylation, survival was significantly improved with chemoradiotherapy (CRT) over radiotherapy (RT) alone (71 vs. 14 weeks, p < 0.01). Furthermore, amongst those treated with temozolomide (TMZ) based CRT, the presence of EGFR amplification, maintenance of PTEN and wild-type p53 and p16 were each associated with trends towards improved survival. Conclusion: MGMT promoter methylation is a strong, independent prognostic factor for OS in GBM. EGFR amplification, maintenance of PTEN, wild-type p53 and p16 all appear to be associated with improved survival in patients treated with CRT. However, the prognostic value of these biomarkers could not be ascertained and larger prospective studies are warranted. Amplification of the epidermal growth factor receptor (EGFR) gene was one of the first genetic alterations identified in the pathogenesis of gliomas 4 and is the target of the small molecule tyrosine kinase inhibitors (TKI) gefitinib and erlotinib. Investigations into the prognostic value of EGFR expression levels have produced mixed results, 5-7 and the effect may be agedependent. 8,9 Phosphatase tensin homolog on chromosome 10 (PTEN) is a tumor suppressor gene closely linked to the EGFR signalling pathway. 10 Loss of PTEN, which occurs in 40-70% of GBM, 11 results in uncontrolled cell proliferation and immortality 10,12 independent of EGFR signalling and has been a...