Colorectal cancer has a high incidence, and approximately 60% of colorectal cancer patients are older than 70, with this incidence likely increasing in the near future. Elderly patients (> 70-75 years of age) are a very heterogeneous group, ranging from the very fit to the very frail. Traditionally, these patients have often been under-treated and recruited less frequently to clinical trials than younger patients, and thus are under-represented in publications about cancer treatment. Recent studies suggest that fit elderly patients can be treated in the same way as their younger counterparts, but the treatment of frail patients with comorbidities is still a matter of controversy. Many factors should be taken into account, including fitness for treatment, the wishes of the patient and family, and quality of life. This review will focus on the existing evidence for surgical, oncologic, and palliative treatment in patients over 70 years old with colorectal cancer. Careful patient assessment is necessary in order to individualize treatment approach, and this should rely on a multidisciplinary process. More well-designed controlled trials are needed in this patient population.

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3538 Background: Addition of (ziv)-aflibercept (A) to FOLFIRI in second-line therapy for metastatic colorectal cancer (CRC) has been shown to be beneficial in phase III VELOUR trial (NCT00561470). A follow-up study (NCT01754272) was undertaken to acquire tumor samples for biomarker analyses and identify subgroups of patients with differential treatment effects. The primary results assessing efficacy according to well-established CRC subgroups defined by RAS, BRAF status and sidedness are reported here. Methods: Tissue specimens were collected for 666 patients from 1226 ITT pts. Suitable specimens were assayed for somatic mutation using NGS targeting extended RAS and BRAF genes. NGS assays with no missing values were obtained for 482 pts. Affymetrix gene chip technology was used for whole-transcriptome profiling; sidedness was extracted from available pathological reports. Differences between subgroups were assessed by interaction analysis. Results: The treatment effects on overall survival (OS) for the 482 pts is still significant HR=0.80 (CI 0.65-0.99), and similar to the ITT (n=1226) results (HR=0.82, CI 0.71-0.93). Two established ways of defining mutations (traditional KRAS exon 2 and extended RAS using NGS) show a trend for a differential effect across mutation groups.(see table for OS). Interestingly, BRAF mutants (which are all RAS wild type) show a trend for better outcome Same is seen for PFS and RR. Sidedness did not affect efficacy (HR: 0.83 (0.63- 1.1) for left and HR: 0.83 (0.54-1.3) for right. Conclusions: None of the mutations subgroup results shows significant interaction, although the ratios of treatment HR favor RAS wild types. Similar trends were observed in published trials with bevacizumab or ramucirumab. Sanofi supported this ISS. Clinical trial information: NCT01754272. [Table: see text]

Background: Despite advances in surgery, radiotherapy, and chemotherapy, pancreatic adenocarcinoma often progresses rapidly and causes death. The physical decline of these patients is expected to impact their quality of life (QoL). Therefore, in addition to objective measures of effectiveness, the evaluation of health-related QoL should be considered a matter of major concern when assessing therapy outcomes. Methods: Observational, prospective, multicenter study including patients with metastatic pancreatic adenocarcinoma who started first-line chemotherapy in 12 Spanish centers. Treatment and clinical characteristics were recorded at baseline. Patients' health-related quality of life, ECOG, and Karnofsky index were measured at baseline, at Days 15 and 30, and every four weeks up to 6 months of chemotherapy. Health-related quality of life was measured using the EORTC-QLQ-C30 and EQ-5D questionnaires. Other endpoints included overall survival and progression-free survival. Results: The study sample included 116 patients (median age of 65 years). Mean (SD) scores for the QLQ-C30 global health status scale showed a significant increasing trend throughout the treatment (p = 0.005). Patients with either a Karnofsky index of 70-80 or ECOG 2 showed greater improvement in the QLQ-C30 global health status score than the corresponding groups with better performance status (p ≤ 0.010). Pain, appetite, sleep disturbance, nausea, and constipation significantly improved throughout the treatment (p < 0.005). Patients with QLQ-C30 global health status scores ≥50 at baseline had significantly greater overall survival and progression-free survival (p = 0.005 and p = 0.021, respectively). No significant associations were observed regarding the EQ-5D score. Conclusions: Most metastatic pancreatic adenocarcinoma patients receiving first-line chemotherapy showed an increase in health-related quality of life scores throughout the treatment. Patients with lower performance status and health-related quality of life at baseline tended to greater improvement. The EORTC QLQ-C30 scale allowed us to measure the health-related quality of life of metastatic pancreatic adenocarcinoma patients receiving first-line chemotherapy.

There is a clear association between the molecular profile of colorectal cancer liver metastases (CRCLM) and the degree to which aggressive progression of the disease impacts patient survival. However, much of our knowledge of the molecular behaviour of colorectal cancer cells comes from experimental studies with, as yet, limited application in clinical practice. In this article, we review the current advances in the understanding of the molecular behaviour of CRCLM and present possible future therapeutic applications. This review focuses on three important steps in CRCLM development, progression and treatment: (1) the dissemination of malignant cells from primary tumours and the seeding to metastatic sites; (2) the response to modern regimens of chemotherapy; and (3) the possibility of predicting early progression and recurrence patterns by molecular analysis in liquid biopsy.