BACKGROUND.The purpose of the current study was to determine whether smoking during chemotherapy or chemoradiation therapy for nonsmall cell lung cancer (NSCLC) affects treatment outcome. METHODS.The authors reviewed the medical records of patients with NSCLC (AJCC Stage III or IV) who were treated with frontline chemotherapy or chemoradiation therapy at the University of Texas M. D. Anderson Cancer Center between January 1993 and December 2002. Treatment type, response, progression-free survival, and overall survival (OS) were correlated with patient demographic characteristics, clinical features, and smoking habits at the time of diagnosis and during therapy. RESULTS.Of 1370 patients who were eligible for analysis, 497 received chemoradiation therapy and 873 received chemotherapy. In the chemoradiation group, 6% of patients were never-smokers, 45% were former smokers, and 49% were current smokers. Multivariate analysis demonstrated no prognostic effect of smoking status on treatment response or OS rates in the chemoradiation therapy group. In the chemotherapy group, 16% of patients were never-smokers, 42% were former smokers, and 42% were current smokers; 20% of patients continued to smoke during therapy. Never-smokers had higher response rates (19% vs. 8% vs. 12%; P ϭ .004) and lower rates of progressive disease (49% vs. 65% vs. 66%; P ϭ .002) than former and current smokers, respectively. The OS rates were found to be higher among never-smokers (P Ͻ.0001), women (P ϭ .002), and those with a better Eastern Cooperative Oncology Group (ECOG) performance status (P Ͻ.0001). The multivariate Cox model indicated that with adjustment for age, gender, stage of disease, and ECOG performance status, the hazard ratio was 1.47 for former smokers (P ϭ .003) and 1.55 for current smokers (P ϭ .0004). Active smoking during therapy did not appear to impact outcome. CONCLUSIONS.Never-smokers were found to have an improved outcome over smokers when treated with chemotherapy.

The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study's conclusion of selection in African Americans before admixture is also subject to doubt. This is because the FST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas.

BACKGROUNDThe authors set out to assess the correlation between smoking‐related second primary tumor (SPT) development and cigarette smoking habits after diagnosis and definitive treatment in patients with early‐stage head and neck squamous cell carcinoma who were enrolled in a placebo‐controlled randomized chemoprevention trial of 13‐cis‐retinoic acid.METHODSLongitudinal data collected for 10 years after the index diagnosis are presented for 1190 patients. Cox proportional hazards regression models were used to examine the effects of changes in smoking behavior on smoking‐related SPT development.RESULTSOne‐third of all patients who quit smoking within 12 months before randomization experienced recurrence, compared with 6.9% and 10.4% of all never‐smokers and former smokers, respectively. Approximately 16% of all current smokers stopped smoking, and nearly 22% of current smokers developed SPTs, compared with 14.5%, 13.2%, and 8.8% of all recent smokers, former smokers, and never‐smokers, respectively. The probability of developing a smoking‐related SPT was highest among patients who were current smokers at randomization. These patients, regardless of whether they ceased smoking during follow‐up, were nearly three times more likely than patients who had never smoked to develop a smoking‐related SPT. In contrast, former smokers and recent quitters who continued to abstain from smoking during follow‐up were approximately 1.5 times more likely to develop an SPT compared with patients who had never smoked.CONCLUSIONSPatients who continue to smoke after the successful treatment of their index head and neck malignancies have a substantially higher risk of developing smoking‐related SPTs. Cancer 2004. © 2004 American Cancer Society.

Deafferentation of the auditory nerve from loss of sensory cells is associated with degeneration of nerve fibers and spiral ganglion neurons (SGN). SGN survival following deafferentation can be enhanced by application of neurotrophic factors (NTF), and NTF can induce the regrowth of SGN peripheral processes. Cochlear prostheses could provide targets for regrowth of afferent peripheral processes, enhancing neural integration of the implant, decreasing stimulation thresholds, and increasing specificity of stimulation. The present study analyzed distribution of afferent and efferent nerve fibers following deafness in guinea pigs using specific markers (parvalbumin for afferents, synaptophysin for efferent fibers) and the effect of brain derived neurotrophic factor (BDNF) in combination with acidic fibroblast growth factor (aFGF). Immediate treatment following deafness was compared with 3‐week‐delayed NTF treatment. Histology of the cochlea with immunohistochemical techniques allowed quantitative analysis of neuron and axonal changes. Effects of NTF were assessed at the light and electron microscopic levels. Chronic BDNF/aFGF resulted in a significantly increased number of afferent peripheral processes in both immediate‐ and delayed‐treatment groups. Outgrowth of afferent nerve fibers into the scala tympani were observed, and SGN densities were found to be higher than in normal hearing animals. These new SGN might have developed from endogenous progenitor/stem cells, recently reported in human and mouse cochlea, under these experimental conditions of deafferentation‐induced stress and NTF treatment. NTF treatment provided no enhanced maintenance of efferent fibers, although some synaptophysin‐positive fibers were detected at atypical sites, suggesting some sprouting of efferent fibers. J. Comp. Neurol. 507:1602–1621, 2008. © 2008 Wiley‐Liss, Inc.