Hypermethylation of the DAP kinase promoter is a common abnormality in early-stage NSCLC. This abnormality is strongly associated with survival, suggesting that DAP kinase plays an important role in determining the biologic aggressiveness of early-stage NSCLC.

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.

There are few studies reporting the incidence of leptomeningeal dissemination (LMD) in patients with glioblastoma; only small case series have been published. Consequently, there are no established standards of care for these patients. Therefore, we undertook this retrospective review to evaluate a large series of patients with glioblastoma treated at MD Anderson Cancer Center to estimate the incidence of LMD and assess the impact of a variety of treatment modalities. Analysis was performed on 595 patients with glioblastoma treated on clinical trials from 2006 to 2012. The diagnosis of LMD was made by imaging or positive cerebrospinal fluid cytology in 24 patients. An additional 12 patients with known LMD diagnosed during this same period were included to evaluate the impact of treatment on outcome for a total of 36 patients. LMD developed in 4.0 % (24/595 patients) of the clinical trial cohort. Median survival from glioblastoma diagnosis was 16.0 months. Estimated median time of glioblastoma diagnosis to LMD was 11.9 months. Median overall survival from the time of LMD diagnosis was 3.5 months. Patients treated for LMD with chemotherapy/targeted therapy and radiation had a significantly prolonged survival (7.7 months) compared to chemotherapy/targeted therapy alone, radiation alone or palliative care. LMD remains an uncommon event in patients with glioblastoma. Patients treated aggressively with chemotherapy/targeted therapy and radiation had the longest median survival following diagnosis of LMD. However, patients receiving chemotherapy/targeted therapy and radiation were younger and this may have influenced survival. Given the overall poor outcomes, improved therapeutic approaches are needed for glioblastoma patients with LMD.

Purpose. Improper storage, use, and disposal of prescribed opioids can lead to diversion or accidental poisoning. Our objective was to determine the patterns of storage, utilization, and disposal of opioids among cancer outpatients. Patients and Methods. We surveyed 300 adult cancer outpatients receiving opioids in our supportive care center and collected information regarding opioid use, storage, and disposal, along with scores on the CAGE (cut down, annoyed, guilty, eye-opener) alcoholism screening questionnaire. Unsafe use was defined as sharing or losing opioids; unsafe storage was defined as storing opioids in plain sight. Results. The median age was 57 years. CAGE was positive in 58 of 300 patients (19%), and 26 (9%) had a history of illicit drug use. Fifty-six (19%) stored opioids in plain sight, 208 (69%) kept opioids hidden but unlocked, and only 28 (9%) locked their opioids. CAGE-positive patients (p 5 .007) and those with a history of illicit drug use (p 5 .0002) or smoking (p 5 .03) were more likely to lock their opioids. Seventy-eight (26%) reported unsafe use by sharing (9%) or losing (17%) their opioids. Patients who were never married or single (odds ratio: 2.92; 95% confidence interval: 1.48-5.77; p 5 .006), were CAGE positive (40% vs. 21%; p 5 .003), or had a history of illicit drug use (42% vs. 23%; p 5 .031) were more likely to use opioids unsafely. Overall, 223 of 300 patients (74%) were unaware of proper opioid disposal methods, and 138 (46%) had unused opioids at home. Conclusion. A large proportion of cancer patients improperly and unsafely use, store, and dispose of opioids, highlighting the need for establishment of easily accessed patient education and drug take-back programs. The Oncologist 2014;19:780-785 Implications for Practice: In our study, a large proportion of cancer outpatients did not store, use, and dispose of opioids safely. Our findings reveal the need for universal education of all patients receiving opioids regarding safety around opioid use to minimize the risks of diversion or accidental poisoning. Strict implementation of patient education resources at the time all opioids are prescribed (by physicians) and dispensed (by pharmacists) could significantly decrease the amount of unused opioids available for diversion or accidental poisoning.

Sixty-one percent of patients with a diagnosis of delirium by a palliative care specialist were missed by the primary referring team. Patients with MD were frequently referred for pain. Universal screening of cancer patients for delirium is recommended.

Background. Palliative care (PC) referrals are often delayed for patients with hematologic malignancies. We examined the differences in attitudes and beliefs toward PC referral between hematologic and solid tumor specialists and how their perception changed with use of the service name "supportive care" (SC). Materials and Methods. We randomly surveyed 120 hematologic and 120 solid tumor oncology specialists at our tertiary care cancer center to examine their attitudes and beliefs toward PC and SC referral. Results. Of the 240 specialists, 182 (76%) responded. Compared with solid tumor specialists, hematologic specialists were less likely to report that they would refer symptomatic patients with newly diagnosed cancer to PC (solid tumor, 43% vs. hematology, 21%; p 5 .002). A significantly greater proportion of specialists expressed that they would refer a patient with newly diagnosed cancer

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance mediated by T790M-independent mechanisms remains a major challenge in the treatment of non-small cell lung cancer (NSCLC). We identified a targetable mechanism of EGFR inhibitor resistance whereby stress hormones activate beta2-adrenergic receptors (β2-AR) on NSCLC cells, which cooperatively signal with mutant EGFR, resulting in the inactivation of the tumor suppressor, liver kinase B1 (LKB1), and subsequently induce IL-6 expression. We show that stress and β2-AR activation promote tumor growth and EGFR inhibitor resistance, which can be abrogated with beta blockers or IL-6 inhibition. IL-6 was associated with worse outcome in EGFR TKI-treated NSCLC patients, and beta blocker use was associated with lower IL-6 concentrations and improved benefit from EGFR inhibitors. These findings provide evidence that chronic stress hormones promote EGFR TKI resistance via β2-AR signaling by an LKB1/CREB/IL-6-dependent mechanism and suggest that combinations of beta blockers with EGFR TKIs merit further investigation as a strategy to abrogate resistance.

The current study was undertaken to evaluate the effect of smoke on forced expiratory volumes and airway responsiveness in wildland fire fighters during a season of active fire fighting. Sixty-three seasonal and full-time wildland fire fighters from five U.S. Department of Agriculture Forest Service (USDAFS) Hotshot crews in Northern California and Montana completed questionnaires, spirometry, and methacholine challenge testing before and after an active season of fire fighting in 1989. There were significant mean individual declines of 0.09, 0.15, and 0.44 L/s in postseason values of FVC, FEV1, and FEF25-75, respectively, compared with preseason values. There were no consistent significant relationships between mean individual declines of the spirometric parameters and the covariates: sex, smoking history, history of asthma or allergies, years as a fire fighter, upper/lower respiratory symptoms, or membership in a particular Hotshot crew. There was a statistically significant increase in airway responsiveness when comparing preseason methacholine dose-response slopes (DRS) with postseason dose-response slopes (p = 0.02). The increase in airway responsiveness appeared to be greatest in fire fighters with a history of lower respiratory symptoms or asthma, but it was not related to smoking history. These data suggest that wildland fire fighting is associated with decreases in lung function and increases in airway responsiveness independent of a history of cigarette smoking. Our findings are consistent with the results of previous studies of municipal fire fighters.