Value of a molecular screening program to support clinical trial enrollment in Asian cancer patients: The Integrated Molecular Analysis of Cancer (IMAC) Study

The value of precision oncology initiatives in Asian contexts remains unresolved. Here, we review the institutional implementation of prospective molecular screening to facilitate accrual of patients into biomarker‐driven clinical trials, and to explore the mutational landscape of advanced tumors occurring in a prospective cohort of Asian patients (n = 396) with diverse cancer types. Next‐generation sequencing (NGS) and routine clinicopathological assays, such as immunohistochemistry, copy number analysis and in situ hybridization tests, were performed on tumor samples. Actionable biomarker results were used to identify eligibility for early‐phase, biomarker‐driven clinical trials. Overall, NGS was successful in 365 of 396 patients (92%), achieving a mean depth of 1,943× and coverage uniformity of 96%. The median turnaround time from sample receipt to return of genomic results was 26.0 days (IQR, 19.0–39.0 days). Reportable mutations were found in 300 of 365 patients (82%). Ninety‐one percent of patients at study enrollment indicated consent to receive incidental findings and willingness to undergo genetic counseling if required. The most commonly mutated oncogenes included KRAS (19%), PIK3CA (16%), EGFR (5%), BRAF (3%) and KIT (3%); while the most frequently mutated tumor suppressor genes included TP53 (40%), SMARCB1 (12%), APC (8%), PTEN (6%) and SMAD4 (5%). Among 23 patients enrolled in genotype‐matched trials, median progression‐free survival was 2.9 months (IQR, 1.5–4.0 months). Nine of 20 evaluable patients (45%; 95% CI, 23.1–68.5%) derived clinical benefit, including 3 partial responses and 6 with stable disease lasting ≥ 8 weeks.     

Associations between frequent headaches, persistent smoking, and attempts to quit

BACKGROUND: Recent studies have found a strong relationship between tobacco smoking and headache pain. It remains unclear whether smoking behavior leads to headache or visa versa, mainly due to the cross-sectional nature of the majority of this research. OBJECTIVE: To help clarify the direction of the relation between smoking and frequent headaches in a representative cohort study. DESIGN AND METHODS: Members of the Dunedin Multidisciplinary Health and Development Study (N=980) were asked about their cigarette smoking and headache history at ages 11 and 13 (childhood), age 15 (mid-adolescence), and age 26 (adulthood). Both cross-sectional and longitudinal associations between smoking and headache status were examined using logistic regression. RESULTS: During mid-adolescence, the likelihood of frequent headaches doubled for smokers relative to nonsmokers (OR: 2.16, 95% CI: 1.39-3.35). Smoking did not increase the risk of developing headaches in adulthood, however. In contrast, individuals who suffered from frequent headaches during mid-adolescence were 2 times more likely to smoke in adulthood than those without headache (OR: 2.20, 95% CI: 1.3-3.7), after controlling for sex and family socioeconomic status. Attempts to quit smoking were significantly more difficult for migraine sufferers with a history of headache than for those with tension-type headache. CONCLUSIONS: Frequent headaches during mid-adolescence appear to increase the risk of daily smoking in adolescence and adulthood. These individuals also have a more difficult time quitting than their headache-free peers.     

Psychological factors after traumatic amputation in landmine survivors: The bridge between physical healing and full recovery

Purpose:?Limb loss due to a landmine injury is sudden and devastating. The resulting disability makes life challenging in a world where physical ability is the ‘norm’. In order to better understand the psychological adjustments individuals make in their recovery from a landmine injury, the Landmine Survivors Network conducted an exploratory qualitative study to determine factors that contribute to an individual's recovery. The study examined psychosocial aspects, coping strategies, and resilience characteristics of limb loss survivors across differing cultural, societal and economic backgrounds.

Method:?Eighty-five participants (68 persons of limb loss, 10 family members, seven service providers) were interviewed using a semi-structured protocol in the USA and an open-ended format in six landmine affected countries. Data analysis was completed using grounded theory analytic strategies.

Results:?Data indicated that the survivors' acceptance of limb loss and their state of psychological recovery were greatly influenced by the individual's resilience characteristics, social support, medical care, economic situation and societal attitudes toward people with disabilities.

Conclusion:?Recovery from traumatic amputation in landmine survivors needs to be comprehensive and coordinated, and requires addressing the individual's physical, psychological, economic and social needs within the context of family, community, and the socio-cultural environment in which they live.