Phase II randomized trial of radiation therapy, cetuximab, and pemetrexed with or without bevacizumab in patients with locally advanced head and neck cancer.

BACKGROUND: We previously reported the safety of concurrent cetuximab, an antibody against epidermal growth factor receptor (EGFR), pemetrexed, and radiation therapy (RT) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In this non-comparative phase II randomized trial, we evaluated this non-platinum combination with or without bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF). PATIENTS AND METHODS: Patients with previously untreated stage III-IVB SCCHN were randomized to receive: conventionally fractionated radiation (70 Gy), concurrent cetuximab, and concurrent pemetrexed (arm A); or the identical regimen plus concurrent bevacizumab followed by bevacizumab maintenance for 24 weeks (arm B). The primary end point was 2-year progression-free survival (PFS), with each arm compared with historical control. Exploratory analyses included the relationship of established prognostic factors to PFS and quality of life (QoL). RESULTS: Seventy-eight patients were randomized: 66 oropharynx (42 HPV-positive, 15 HPV-negative, 9 unknown) and 12 larynx; 38 (49%) had heavy tobacco exposure. Two-year PFS was 79% [90% confidence interval (CI) 0.69-0.92; P < 0.0001] for arm A and 75% (90% CI 0.64-0.88; P < 0.0001) for arm B, both higher than historical control. No differences in PFS were observed for stage, tobacco history, HPV status, or type of center (community versus academic). A significantly increased rate of hemorrhage occurred in arm B. SCCHN-specific QoL declined acutely, with marked improvement but residual symptom burden 1 year post-treatment. CONCLUSIONS: RT with a concurrent non-platinum regimen of cetuximab and pemetrexed is feasible in academic and community settings, demonstrating expected toxicities and promising efficacy. Adding bevacizumab increased toxicity without apparent improvement in efficacy, countering the hypothesis that dual EGFR-VEGF targeting would overcome radiation resistance, and enhance clinical benefit. Further development of cetuximab, pemetrexed, and RT will require additional prospective study in defined, high-risk populations where treatment intensification is justified.

Predictors and outcomes of health-related quality of life in caregivers of cardiothoracic transplant recipients.

Cardiothoracic transplant programs generally require that transplant recipients have family caregivers to assist them posttransplant. The burden of caregiving on the family members remains poorly understood. If caregivers' well-being is compromised by caregiving, it may bode poorly for transplant recipients' own health in the long-term posttransplant. We examined caregiver health-related quality of life (HRQOL) during the first year after their family member's transplant, its predictors and its relationship to subsequent patient survival. Adult (aged 18+) caregivers of 242 cardiothoracic transplant recipients (lung = 134; heart = 108) completed assessments of demographics, psychosocial characteristics and caregiver burden at 2 months posttransplant, and HRQOL at 2, 7 and 12 months posttransplant. Recipients' survival time was obtained from medical records. Caregiver HRQOL was generally high across the first-year posttransplant in emotional and social functioning; caregiver physical functioning significantly worsened. There were no differences by type of recipient transplant. Greater caregiver burden predicted poorer caregiver HRQOL in several physical domains at 12 months posttransplant. Transplant recipients whose caregivers had lower perceived general health at 12 months posttransplant showed poorer survival rates during the subsequent 7 years of follow up. Transplant teams should identify those caregivers at risk for poorer general health posttransplant to maximize positive outcomes for the entire family.

Predictors of posttraumatic stress among victims of motor vehicle accidents.

OBJECTIVE: This study identified factors that predict individual vulnerability to psychological trauma by examining the relationships among situation and person variables and symptoms of posttraumatic stress disorder (PTSD) 1, 6, and 12 months after a serious motor vehicle accident (MVA). METHODS: Background characteristics, exposure variables (ie, injury severity and accident characteristics), and psychosocial variables (ie, perceived loss of control, social support, and coping) were used to predict symptoms of PTSD and recovery in 115 injured MVA victims. All participants were injured during the MVA and provided data prospectively over the course of a year after their accidents. RESULTS: Along with background and exposure variables, use of wishful thinking coping distinguished between victims with and without symptoms of PTSD. CONCLUSIONS: Psychosocial variables such as wishful thinking coping can be used to identify MVA victims who are at risk of developing chronic posttraumatic stress and warrant further investigation.

Health psychology: mapping biobehavioral contributions to health and illness.

Our evolving understanding of how psychosocial and behavioral factors affect health and disease processes has been marked by investigation of specific relationships and mechanisms underlying them. Stress and other emotional responses are components of complex interactions of genetic, physiological, behavioral, and environmental factors that affect the body's ability to remain or become healthy or to resist or overcome disease. Regulated by nervous, endocrine, and immune systems, and exerting powerful influence on other bodily systems and key health-relevant behaviors, stress and emotion appear to have important implications for the initiation or progression of cancer, HIV, cardiovascular disease, and other illnesses. Health-enhancing and health-impairing behaviors, including diet, exercise, tobacco use, and protection from the sun, can compromise or benefit health and are directed by a number of influences as well. Finally, health behaviors related to being ill or trying to avoid disease or its severest consequences are important. Seeking care and adhering to medical regimens and recommendations for disease surveillance allow for earlier identification of health threats and more effective treatment. Evidence that biobehavioral factors are linked to health in integrated, complex ways continues to mount, and knowledge of these influences has implications for medical outcomes and health care practice.