Focus & Scope

The Neuro-Psychological Axis of Smoking-Associated Cancer

Hildegard M Schuller*

Department of Biomedical & Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA

This mini-review summarizes current knowledge on similarities and synergism between smoking and psychological stress-induced modulations of growth stimulating and inhibiting regulatory networks in epithelial cells and epithelial cancers with emphasis on cancer stimulating neurotransmitters and their receptors as well as cancer inhibiting γ-aminobutyric acid (GABA) and opioids. Hyperactive cAMP signaling downstream of beta-adrenergic receptors (β-ARs) has been identified as the driving force of most smoking-associated cancers by numerous preclinical studies and psychological stress intensifies these effects while experimental stress reduction inhibits. The integration of cAMP reduction via stress reduction by pharmacological and psychological means such as psychotherapy, relaxation meditation and yoga into any cancer treatment strategy is recommended.

Time from Stereotactic Radiotherapy to Immunotherapy Is a Predictor for Outcome in Stage IV Non-Small Cell Lung Cancer

Rodney E. Wegner¹*, Stephen Abel¹, Shaakir Hasan¹, Richard J. White¹, Gene Finley², Dulabh Monga², Athanasios Colonias¹, Vivek Verma¹

¹Allegheny Health Network Cancer Institute, Division of Radiation Oncology, USA

²Allegheny Health Network Cancer Institute, Division of Medical Oncology, USA

Immunotherapy (IMT) has revolutionized the treatment of stage IV non-small cell lung cancer (NSCLC). However, optimal timing of IMT in relation to stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) is unknown. Utilizing the National Cancer Database, we examined trends in IMT use in metastatic NSCLC patients and the potential survival implications of IMT timing in relation to SBRT/SRS. We queried the NCDB for patients with Stage IV NSCLC diagnosed between 2004-2015. Patients receiving IMT and SBRT/SRS to any site were included. Multivariate logistic regression identified predictors of IMT use. Receiver operator characteristic curve analysis determined an a priori timeframe between SBRT and IMT predictive of optimal overall survival (OS). Univariate and multivariate analyses identified factors predictive of OS. Propensity-adjusted Cox proportional hazard ratios were used to mitigate indication bias. Of 13,862 eligible patients, 371 received IMT. The majority (75%) received chemotherapy. IMT use was associated with improved median OS on univariate analysis (17 vs. 13 months, p<0.0001). Adenocarcinoma histology, chemotherapy use, and recent treatment year were associated with IMT. On multivariate propensity-adjusted Cox regression, predictors for improved OS included: younger age, lower comorbidity score, lower grade, private insurance, IMT use, and female sex. Patients treated ≥ 21 days (a priori threshold) after SBRT/SRS initiation had improved median OS (19 vs. 15 months, p=0.0335). In patients with Stage IV NSCLC, IMT use following SBRT/SRS has increased. OS improved when IMT was given ≥3 weeks after initiating SBRT/SRS; suggesting a potential optimal time-frame between RT and IMT.

Detection of Antigen-Specific T Cell Lineages and Effector Functions Based on Secretory Signature

Greg A. Kirchenbaum, Jodi Hanson, Diana R. Roen, Paul V. Lehmann*

Cellular Technology Limited (CTL) Shaker Heights, OH, 44122-5350, USA

T cells not only protect us from infectious diseases and cancer, but are also involved in transplant rejection, autoimmune diseases, and allergies. Each of these immunologic processes share a common link in which antigen-specific T cells undergo expansion, with some of the resulting progeny differentiating into memory cells. Memory T cells belong to several distinct lineages, and sub-lineages, that fundamentally differ in their effector functions and capacity to mediate a protective or pathological immune response. In this mini-review, we outline how such memory T cell subpopulations can readily be identified on the basis of their secretory signature using a multi-color ImmunoSpot® assay.

National Trends in the Use of Targeted Therapy and Immunotherapy in the Up Front Management of Glioblastoma

Richard White¹, Stephen Abel², Shaakir Hasan², Vivek Verma², Tulika Ranjan³, Stephen M. Karlovits², Rodney E Wegner²*

¹Allegheny Health Network, Department of Internal Medicine, Pittsburgh, PA, USA

²Allegheny Health Network Cancer Institute, Division of Radiation Oncology, Pittsburgh, PA, USA

³Allegheny Health Network Cancer Institute, Division of Neuro Oncology, Pittsburgh, PA, USA

Glioblastoma (GBM) carries an abysmal prognosis. Current standard of care involves an aggressive multimodality approach including surgical resection followed by adjuvant chemoradiation. Despite this approach, overall survival remains poor and treatment approaches continue to evolve. Given the successes of immunotherapy in other disease sites, implementation in GBM management may improve outcomes. We conducted this retrospective National Cancer Database (NCDB) study to analyze treatment trends and outcomes from 2004-2015 regarding immunotherapy for GBM and queried for patients diagnosed between 2004-2015 with GBM and excluded patients treated without surgery, extracranial radiation, or chemotherapy as well as those lost to follow up.

Of the 39,317 eligible patients in this study, 511 were treated with immunotherapy and 38,806 lack thereof. Median overall survival for all patients was 15 months with a 2 and 5 year survival rate of 29% and 8%, respectively. Factors positively influencing delivery of immunotherapy included younger age, higher income, facility location in a metropolitan location, greater distance to the treatment facility, treatment at an academic facility, treatment outside of the years 2007 to 2009, and Caucasian race. On propensity matched analysis, survival was 18 months and 17 months with and without immunotherapy, respectively (p=0.15). Higher comorbidity, lower income, and male gender predicted for worse survival.

The results of the NCDB analysis showed an initial decrease and then increase in the use of immunotherapy in the management of GBM. Propensity-matched analyses did not show an overall survival benefit.