Predicting response to treatment in gastroesophageal junction adenocarcinomas: combining clinical, imaging, and molecular biomarkers.

The incidence of adenocarcinomas of the gastroesophageal junction (GEJ) is rapidly rising, and even in early-stage locoregional confined disease the 5-year survival rate rarely exceeds 25%-35%. Randomized trials and meta-analyses have demonstrated a benefit with neoadjuvant or perioperative chemotherapy and with neoadjuvant chemoradiotherapy. However, the optimal approach in individual patients is not clear and remains controversial. A consistent finding is that patients who have a histopathological response to neoadjuvant therapy are more likely to receive a survival benefit. These clinical data provide a strong argument for the urgent development of methods to predict histopathological response to neoadjuvant therapies for GEJ adenocarcinoma. Published data demonstrate that clinicopathological features (tumor location), imaging (fluorodeoxyglucose-positron emission tomography "metabolic response"), and tissue/molecular biomarkers may all have a predictive value for neoadjuvant therapies. However, it is uncertain from published data whether or not they will be useful for clinical decision making in individual patients. Existing candidate biomarkers need to be properly qualified and validated and novel biomarkers are required; and an optimal approach should involve the combination and integration of clinical, imaging, and molecular biomarkers. This review presents the evidence base and discusses novel experimental approaches for the combination of biomarker modalities to allow optimization of an individualized treatment approach in GEJ adenocarcinoma patients that may be relevant to other tumor types as well.

Quality of Life in healthy old age: relationships with childhood IQ, minor psychological symptoms and optimism.

BACKGROUND: The aim of this study was to examine relationships in old age between Quality of Life (QoL), childhood IQ, current cognitive performance and minor psychological symptoms, and to estimate possible contributions to these relationships made by sex, education, socioeconomic deprivation, current living group, sex, and balance and 6m walk time. METHODS: We conducted a follow-up study on 88 community residents without dementia who were survivors of the Aberdeen City 1921 birth cohort. QoL was measured by the Schedule for the Evaluation of Individual QoL-Direct Weighting (SEIQoL-DW), current cognition by MMSE and Raven's Progressive Matrices (RPM), childhood IQ, minor psychological symptoms as assessed by the Hospital Anxiety and Depression Scale (HADS), and optimism by the Life Orientation Test (LOT); we included balance, 6m walk time and demographic data. RESULTS: QoL was better in men than in women. Women reported more anxiety and depression. QoL correlated significantly with current cognition measured by RPM, childhood intelligence, anxiety and depressive symptoms, optimism and balance. The best model to predict QoL relied on childhood intelligence (13.4% of the variance) and was improved by addition of HADS (8.8 %) and LOT (4.8 %). Other variables did not contribute to the prediction of QoL. CONCLUSION: In the absence of dementia, childhood IQ, HADS and LOT explain 26.9% of the variance in QoL as reported by community-resident old people. The direction of association between current anxiety and depressive symptoms and lower QoL is uncertain. Lower childhood IQ may contribute to coping less well with later life. Lower QoL is not an invariable concomitant of mild cognitive decline.