A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial.

BACKGROUND: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. PATIENTS AND METHODS: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). RESULTS: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. CONCLUSIONS: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.

Clinical utility of portable electrophysiology to measure fatigue in treatment-naïve non-small cell lung cancer.

PURPOSE: Cancer-related fatigue (CRF) biology remains poorly understood. Responsible mechanisms may be central or peripheral and originate anywhere from the brain to muscle fiber. Objective measurement is complex and previously limited to specialized laboratories. Portable electroencephalography (EEG) and electromyography (EMG) may enhance objective measurement. This study evaluated the feasibility and acceptability of portable EMG-EEG in CRF assessment. METHODS: A prospective observational feasibility study compared ten outpatients with inoperable, treatment-naïve non-small cell lung cancer and CRF to ten healthy volunteers. All completed a sustained isometric hand-grip contraction at 30% maximal level until self-perceived exhaustion. 128-channel EEG and 2-channel EMG signals of forearm muscles were recorded. Device acceptability was evaluated by questionnaire. RESULTS: The task was evaluated in two stages; first and last 20 s. CRF cohort perceived exhaustion earlier than volunteers (mean 137 ± 76 s vs 208 ± 51 s). As fatigue progressed, EMG amplitude increased significantly (CRF p = 0.02; volunteers: p = 0.04) in both groups as did EMG beta band power (CRF p = 0.008; volunteers: p = 0.006). The increase was significantly less in CRF (amplitude p = 0.032; beta power: p = 0.014). EEG beta band power in the contralateral motor cortex increased significantly (CRF p = 0.03; volunteers: p = 0.019) in both cohorts but to greater extent (p = 0.024) in CRF. One hundred percent device acceptability was reported. CONCLUSIONS: A laboratory-based evaluation was successfully adapted to the outpatient setting during routine visits. High acceptability supports clinical utility. In CRF, a higher degree of cortical activation was required to drive a much lower level of muscle performance. This suggests impairment of both central and peripheral mechanisms in CRF.

ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS).

BACKGROUND: Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens. METHODS: This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research. DISCUSSION: This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG). TRIAL REGISTRATION: NCT01726452 . Protocol 10-14. Date of registration 06/11/2012.

Patient preference: a comparison of electronic patient-completed questionnaires with paper among cancer patients.

In this study, we compared cancer patients preference for computerised (tablet/web-based) surveys versus paper. We also assessed whether the understanding of a cancer-related topic, pharmacogenomics is affected by the survey format, and examined differences in demographic and medical characteristics which may affect patient preference and understanding. Three hundred and four cancer patients completed a tablet-administered survey and another 153 patients completed a paper-based survey. Patients who participated in the tablet survey were questioned regarding their preference for survey format administration (paper, tablet and web-based). Understanding was assessed with a 'direct' method, by asking patients to assess their understanding of genetic testing, and with a 'composite' score. Patients preferred administration with tablet (71%) compared with web-based (12%) and paper (17%). Patients <65 years old, non-Caucasians and white-collar professionals significantly preferred the computerised format following multivariate analysis. There was no significant difference in understanding between the paper and tablet survey with direct questioning or composite score. Age (<65 years) and white-collar professionals were associated with increased understanding (both P = 0.03). There was no significant difference in understanding between the tablet and print survey in a multivariate analysis. Patients overwhelmingly preferred computerised surveys and understanding of pharmacogenomics was not affected by survey format.

Impact of smoking status on the relative efficacy of the EGFR TKI/angiogenesis inhibitor combination therapy in advanced NSCLC-a systematic review and meta-analysis.

BACKGROUND: The ETOP 10-16 BOOSTER trial failed to demonstrate a progression-free survival (PFS) benefit for adding bevacizumab to osimertinib in second line. An exploratory subgroup analysis, however, suggested a PFS benefit of the combination in patients with a smoking history and prompted us to do this study. METHODS: A systematic review and meta-analysis to evaluate the differential effect of smoking status on the benefit of adding an angiogenesis inhibitor to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor therapy was carried out. All relevant randomized controlled trials appearing in main oncology congresses or in PubMed as of 1 November 2021 were used according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Primarily PFS according to smoking status, and secondarily overall survival (OS) were of interest. Pooled and interaction hazard ratios (HRs) were estimated by fixed or random effects models, depending on the detected degree of heterogeneity. Bias was assessed using the revised Cochrane tool for randomized controlled trials (RoB 2). RESULTS: Information by smoking was available for 1291 patients for PFS (seven studies) and 678 patients for OS (four studies). The risk of bias was low for all studies. Combination treatment significantly prolonged PFS for smokers [n = 502, HR = 0.55, 95% confidence interval (CI): 0.44-0.69] but not for nonsmokers (n = 789, HR = 0.92, 95% CI: 0.66-1.27; treatment-by-smoking interaction P = 0.02). Similarly, a significant OS benefit was found for smokers (n = 271, HR = 0.66, 95% CI: 0.47-0.93) but not for nonsmokers (n = 407, HR = 1.07, 95% CI: 0.82-1.42; treatment-by-smoking interaction P = 0.03). CONCLUSION: In advanced EGFR-non-small-cell lung cancer patients, the addition of an angiogenesis inhibitor to EGFR-tyrosine kinase inhibitor therapy provides a statistically significant PFS and OS benefit in smokers, but not in non-smokers. The biological basis for this observation should be pursued and could determine whether this might be due to a specific co-mutational pattern produced by tobacco exposure.

IGF-I treatment improves the functional properties of fast- and slow-twitch skeletal muscles from dystrophic mice.

Although insulin-like growth factor-I (IGF-I) has been proposed for use by patients suffering from muscle wasting conditions, few studies have investigated the functional properties of dystrophic skeletal muscle following IGF-I treatment. 129P1 ReJ-Lama2(dy) (129 ReJ dy/dy) dystrophic mice suffer from a deficiency in the structural protein, laminin, and exhibit severe muscle wasting and weakness. We tested the hypothesis that 4 weeks of IGF-I treatment ( approximately 2 mg/kg body mass, 50 g/h via mini-osmotic pump, subcutaneously) would increase the mass and force producing capacity of skeletal muscles from dystrophic mice. IGF-I treatment increased the mass of the extensor digitorum longus (EDL) and soleus muscles of dystrophic mice by 20 and 29%, respectively, compared with untreated dystrophic mice (administered saline-vehicle only). Absolute maximum force (P(o)) of the EDL and soleus muscle was increased by 40 and 32%, respectively, following IGF-I treatment. Specific P(o) (sP(o)) was increased by 23% in the EDL muscles of treated compared with untreated mice, but in the soleus muscle sP(o) was unchanged. IGF-I treatment increased the proportion of type IIB and type IIA fibres and decreased the proportion of type I fibres in the EDL muscles of dystrophic mice. In the soleus muscles of dystrophic mice, IGF-I treatment increased the proportion of type IIA fibres and decreased the proportion of type I fibres. Average fibre cross-sectional area was increased in the EDL and soleus muscles of treated compared with untreated mice. We conclude that IGF-I treatment ameliorates muscle wasting and improves the functional properties of skeletal muscles of dystrophic mice. The findings have important implications for the role of IGF-I in ameliorating muscle wasting associated with the muscular dystrophies.

Influence of race on diagnosis in adolescent psychiatric inpatients.

OBJECTIVE: To examine racial differences in 352 psychiatric inpatients, aged 12 to 18 years, at a state hospital facility that accepted admissions from throughout South Carolina. These were all the adolescent admissions during an entire calendar year (1988). There were 101 African-American and 251 white subjects. METHOD: The data were abstracted from patients' hospital medical records and nursing incident reports. DSM-III-R discharge diagnoses were assigned to five non-mutually exclusive groupings (organic/psychotic, mood/anxiety, disruptive, personality, substance abuse). Racial differences were analyzed using chi 2, logistic regression, and T statistics. RESULTS: African-Americans were more likely to be involuntarily committed at the time of admission (p = .010). Organic/psychotic diagnoses were much more frequent in African-Americans (odds ratio = 3.15, p < .003). Whites (p = .0347) were almost two times more likely to receive mood/anxiety diagnoses even when controlling for gender, type of admission, and comorbid diagnoses. Substance abuse was more often diagnosed in whites (odds ratio = 5.46, p < .0001). CONCLUSIONS: This study identifies significant racial differences in the discharge diagnoses of psychiatrically hospitalized adolescents. African-Americans have fewer mood/anxiety and substance abuse diagnoses but significantly more organic/psychotic diagnoses. Some of these differences may reflect ethnocentric clinician bias in the diagnostic assessment of youth from differing cultural/racial backgrounds.

Race and gender differences in the treatment of psychiatric disorders in young adolescents.

OBJECTIVE: Most children and adolescents with mental illness remain untreated. Evidence suggests that race is a factor in the referral of children for treatment. This study examines race and gender differences in treatment of adolescent psychiatric disorders. METHOD: During a two-stage, school-based, epidemiological study of depression, data were collected on 478 adolescents. Instruments included the Schedule for Affective Disorders and Schizophrenia for School-Age Children and the Children's Global Assessment Scale. RESULTS: Twenty-two percent of the sample had contact with professionals during the prior year, including 56% of adolescents with a psychiatric diagnosis. Significant odds ratios (ORs) were found between all diagnoses and treatment. Trends for undertreatment of females and African-Americans were evident in univariable and multivariable models. The OR (0.34) for African-American females was significant in the multivariable model. African-Americans were significantly more likely to receive only one or two treatment contacts. CONCLUSION: Data suggest race and gender differences in the treatment of adolescent psychiatric disorders. Possible explanations include referral bias, low cultural competence of mental health professionals, and cultural differences in the expression and tolerance of symptoms and help-seeking behaviors. Further study of factors influencing treatment decisions is needed.

Prevalence of attention-deficit/hyperactivity disorder in a community sample of older adolescents.

OBJECTIVE: To study the prevalence and correlates of attention-deficit/hyperactivity disorder (ADHD) in a community sample of older adolescents. METHOD: From 1986 to 1988, 3,419 seventh, eighth, and ninth graders were screened with the Center for Epidemiologic Studies-Depression Scale. The top decile scorers and a random sample of the remainder were interviewed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children. These data are from the second wave of interviews (N = 490, mean age = 18.65). RESULTS: The weighted prevalence of DSM-III-R ADHD was 1.51% (males: 2.62%, females: 0.54%). Significant associations (p < .05) were found for gender (male), comorbid affective disorders, baseline undesirable life events, and fewer than two biological parents at baseline. Family cohesion (p = .058) is inversely associated with ADHD. For subjects not meeting the age-at-onset criterion, 1.94% met the eight symptom criteria, and females (3.2%) were more prevalent than males (0.3%). CONCLUSIONS: ADHD remains a problem in this sample of older adolescents and is often comorbid with affective disorders. A significant number report eight ADHD symptoms but do not meet the age-at-onset criterion. This group deserves research attention.

Incidence of major depressive disorder and dysthymia in young adolescents.

OBJECTIVE: An epidemiological study conducted between 1987 and 1989 in a single school district in the southeastern United States investigated the incidence, transition probabilities, and risk factors for major depressive disorder (MDD) and dysthymia in adolescents aged 11 to 16 years. METHOD: Diagnoses were based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children, which was administered to 247 mother-adolescent pairs at 12-month intervals. RESULTS: One-year MDD and dysthymia incidences were 3.3% (n = 11) and 3.4% (n = 9), respectively. Transition probabilities demonstrated movement from disorder to no disorder over time. Family cohesion (odds ratio = 0.95) was the only significant predictor of incident MDD. No factors were significant for dysthymia. While baseline MDD was a significant risk factor for depression at follow-up, 80% of subjects with baseline MDD did not meet the criteria for diagnosis at follow-up. CONCLUSION: Findings suggest perceived family support or cohesion may be more important to adolescent mental health than family structure.

Prevalence of PTSD in a community sample of older adolescents.

OBJECTIVE: To examine prevalence and correlates of trauma and posttraumatic stress disorder (PTSD) symptoms and diagnosis in older adolescents aged 16 through 22 years. METHOD: The second cycle of a longitudinal epidemiological study in the Southeast included a semistructured interview assessing PTSD symptomatology administered to 490 adolescents. RESULTS: Approximately 3% of female subjects and 1% of male subjects satisfied the DSM-IV criteria for PTSD. Females reported more traumatic events than males, and black subjects reported more events than white subjects. Being female (odds ratio = 12.32), experiencing rape or child sexual abuse (odds ratio = 49.37), and witnessing an accident or medical emergency (odds ratio = 85.02) were associated with increased risk of PTSD. CONCLUSIONS: While relatively few adolescents satisfy the criteria for PTSD, most subjects who experienced a traumatic event reported some PTSD symptoms. Specific types of traumatic events were associated with occurrence of PTSD.

Frequency of obsessive-compulsive disorder in a community sample of young adolescents.

OBJECTIVE: To investigate the frequency and phenomenology of obsessive-compulsive disorder (OCD) and subclinical OCD in young adolescents. METHOD: A two-stage epidemiological study originally designed to investigate adolescent depression was conducted between 1986 and 1988 in the southeastern United States. In the first stage, a self-report depressive symptom questionnaire was administered to a community sample of 3,283 adolescents. In the diagnostic stage, the Schedule for Affective Disorders and Schizophrenia for School-Age Children and the Children's Global Assessment Scale were administered to 488 mother-child pairs. RESULTS: The prevalences of OCD and subclinical OCD were found to be 3% and 19%, respectively. Prevalences were similar in males and females. Females reported more symptoms of compulsions although males reported more obsessions. About 55% of adolescents with OCD reported both obsessions and compulsions. The most common compulsions were arranging (56%), counting (41%), collecting (38%), and washing (17%). Major depressive disorder (45%), separation anxiety (34%), dysthymia (29%), suicidal ideation (15%), and phobia (8%) were the diagnoses most frequently comorbid with OCD. CONCLUSIONS: Findings suggest that OCD is not infrequent among adolescents and that the characteristic comorbidity and symptomatology of OCD may facilitate earlier identification and treatment by clinicians.

Frequency of phobic disorder in a community sample of young adolescents.

OBJECTIVE: To investigate the frequency and phenomenology of clinical, subsyndromal, and subthreshold phobias in young adolescents. METHODS: A two-stage epidemiological study originally designed to investigate adolescent depression was conducted between 1986 and 1988 in the southeastern United States. In the first stage, a self-report depressive symptom questionnaire was administered to a community sample of 3,283 adolescents. In the diagnostic stage, the Schedule for Affective Disorders and Schizophrenia for School-Age Children and the Children's Global Assessment Scale were administered to 487 mother-child pairs. RESULTS: Prevalence rates of clinical, subsyndromal, and subthreshold phobia were 2.3%, 14.5%, and 22.2%, respectively. One-year incidence rates were 0.4%, 8.0%, and 16.9%, with 43.0% of phobic subjects categorized at the same or a more severe level after a year. Females, blacks, subjects not living with both biological parents, and older adolescents were more likely to meet the diagnostic criteria for clinical phobia. The majority (77%) of subjects with clinical phobia experienced multiple phobias. Subsyndromal (52%) and subthreshold (74%) phobics were more likely to experience simple phobias only. CONCLUSIONS: Phobic symptoms are relatively common at a moderate level and in the majority of adolescents are somewhat transitory in nature. Characteristic symptomatology and comorbidity may facilitate earlier identification of subjects at risk of persistent symptomatology and in need of treatment.

Incidence and predictors of suicidal behaviors in a longitudinal sample of young adolescents.

OBJECTIVE: This analysis examines 1-year transition probabilities and baseline predictors for suicidal behaviors in young adolescents. METHOD: Adolescents from a two-stage, community-based longitudinal study were classified into suicidal behavior categories (attempt, plan, ideation, and none) for baseline and follow-up years. Transition probabilities for movement among categories were calculated, and polytomous logistic regression analysis was used to examine predictors of suicidal behaviors. RESULTS: Among those with no suicidal behaviors at baseline, 1-year incidence rates were 1.3% for attempts and 1.7% each for plans and ideation. Increasing family cohesion was protective for suicide attempts (odds ratio [OR] = 0.9). Female subjects were more likely than males to report plans (OR = 8.9) and ideation (OR = 4.1). Increasing impulsivity (OR = 2.3), prior suicidal behavior (OR = 10.6), and undesirable life events (OR = 1.1) were significant predictors of plans. CONCLUSIONS: While there are a number of predictors of suicidal behaviors, the false-positive rate is high. Focusing on proximal risk factors, particularly stressors in adolescent development, may overlook the fundamental role of underlying mental disorder and familial factors--both biological and environmental. Suicide and suicidal behaviors are the result of a constellation of adverse factors requiring a range of interventions for prevention.

Incidence of obsessive-compulsive disorder in a community sample of young adolescents.

OBJECTIVE: To investigate the incidence, transition probabilities, and risk factors for obsessive-compulsive disorder (OCD) and subclinical OCD in adolescents. METHOD: A two-stage epidemiological study originally designed to investigate depression was conducted between 1987 and 1989 in the southeastern United States. For the screening, a self-report depressive symptom questionnaire was administered to a community sample of 3,283 adolescents. In the diagnostic stage, the Schedule for Affective Disorders and Schizophrenia for School-Age Children was administered to 488 mother-child pairs. Baseline screening and diagnostic data from the first year the subject completed an interview and follow-up diagnostic data from subsequent years were used. RESULTS: The 1-year incidence rates of OCD and subclinical OCD were found to be 0.7% and 8.4%, respectively. Transition probabilities demonstrated a pattern of moving from more severe to less severe categories. Of those with baseline OCD, 17% had the diagnosis of OCD at follow-up; 62% moved to the referent group. Of those with baseline subclinical OCD, 1.5% had OCD at follow-up and 75% moved to the referent group. Black race (odds ratio [OR] = 23.38), age (OR = 4.02), desirable life events (OR = 0.78), undesirable life events (OR = 1.21), and socioeconomic status (OR not estimable) were significant predictors of incident OCD. Age (OR = 2.30), desirable life events (OR = 0.92), and undesirable life events (OR = 1.13) were significantly associated with incident subclinical OCD. CONCLUSION: An initial diagnosis of subclinical OCD was not significantly predictive of a diagnosis of OCD at 1-year follow-up. The overall morbidity remained higher at follow-up in the baseline OCD group than in the baseline subclinical OCD group. The baseline subclinical OCD group was more dysfunctional at follow-up than was the baseline referent group. Further research concerning differences in symptomatology and impairment between OCD and subclinical OCD is warranted.

Dual diagnosis and successful participation of adolescents in substance abuse treatment.

A retrospective record review of one year of admissions to a residential adolescent substance abuse treatment program (N = 91) examined the prevalence of comorbid psychiatric disorders and factors associated with successful treatment participation. Psychiatric and substance use disorders (SUD) were diagnosed by DSM-IV criteria. Successful participation was based on multiple factors assessed by the treatment team. Consistent with prior studies, there was considerable comorbidity (63.7%) with both disruptive (Attention Deficit Hyperactivity Disorder [ADHD], 11%; Conduct Disorder [CD], 24%) and other disorders (depression, 24%; adjustment disorder, 7.7%; bipolar disorder, 3.3%). Male gender was negatively associated (OR = 0.23, P = 0.019) with successful participation in univariate analyses, as was ADHD (OR = 0.18, P = 0.007). CD (OR = 0.37, P = 0.053) approached significance. Multivariate analysis reveals ADHD was significant while having CD and being male approached significance. Psychotropic medication use and other diagnoses were not associated with successful participation. It is concluded that further research on the relationship between ADHD, CD, and substance abuse treatment is needed.

A longitudinal study of adolescent mental health service use.

This study examines longitudinal mental health service use patterns of a school-based sample of adolescents. Based on the Center for Epidemiologic Studies Depression Scale scores, a stratified sample of middle-school students was interviewed using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children: cycle one (n = 579; mean age 12.83) and cycle two (n = 490; mean age 18.65). Service use also was assessed by mailed questionnaire: cycle three (n = 330; mean age 20.60). Service use decreased over time. Whites and males received significantly more treatment in the first cycle. In the second cycle, service use by race and gender was equal; in the third cycle, females received more treatment. Those with a psychiatric diagnosis (first cycle, 54%; second cycle, 33%) received treatment in the prior year. Under-treatment of youth with psychiatric diagnoses is a significant problem, with differences in service use by race and gender over time.

Overexpression of the mammalian target of rapamycin (mTOR) and angioinvasion are poor prognostic factors in early stage NSCLC: a verification study.

BACKGROUND: A recent study by Dhillon et al. [12], identified both angioinvasion and mTOR as prognostic biomarkers for poor survival in early stage NSCLC. The aim of this study was to verify the above study by examining the angioinvasion and mTOR expression profile in a cohort of early stage NSCLC patients and correlate the results to patient clinico-pathological data and survival. METHODS: Angioinvasion was routinely recorded by the pathologist at the initial assessment of the tumor following resection. mTOR was evaluated in 141 early stage (IA-IIB) NSCLC patients (67 - squamous; 60 - adenocarcinoma; 14 - others) using immunohistochemistry (IHC) analysis with an immunohistochemical score (IHS) calculated (% positive cells×staining intensity). Intensity was scored as follows: 0 (negative); 1+ (weak); 2+ (moderate); 3+ (strong). The range of scores was 0-300. Based on the previous study a cut-off score of 30 was used to define positive versus negative patients. The impact of angioinvasion and mTOR expression on prognosis was then evaluated. RESULTS: 101 of the 141 tumors studied expressed mTOR. There was no difference in mTOR expression between squamous cell carcinoma and adenocarcinoma. Angioinvasion (p=0.024) and mTOR staining (p=0.048) were significant univariate predictors of poor survival. Both remained significant after multivariate analysis (p=0.037 and p=0.020, respectively). CONCLUSIONS: Our findings verify angioinvasion and mTOR expression as new biomarkers for poor outcome in patients with early stage NSCLC. mTOR expressing patients may benefit from novel therapies targeting the mTOR survival pathway.

The influence of race and gender on depressive and substance abuse symptoms in high-risk adolescents.

Concerns about the cultural competence of child mental health services has led to the examination of racial/ethnic and gender differences in the prevalence of psychiatric symptoms. This study examines racial and gender differences in depressive and substance abuse symptomatology in a high-risk population of adolescents living in five residential group homes in South Carolina. We surveyed 299 youth ages 12 to 17, including 101 African American and 198 Whites. They completed the Centers for Epidemiological Studies-Depression scale (CES-D) and questions on substance abuse, demographics, and psychosocial functioning. No significant differences were found in the percentages of Whites and African Americans scoring above 16+ and 23+ cutoff scores on the CES-D, but significant gender differences were identified. Neither race nor race by age group interactions were found to be significantly correlated in regression analyses with CES-D score nor multiple substance use, whereas gender (p < .001) and school performance were significantly correlated with CES-D score, and poverty was correlated with multiple substance use. Our results indicate that levels of depressive symptomatology as measured by the CES-D are much more sensitive to gender than to race in high-risk populations. Different gender cutoffs are indicated when using systematic instruments in the measurement of depressive symptoms.