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.
DOI: 10.29245/2578-3009/2019/2.1171 View / Download Pdf 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.
DOI: 10.29245/2578-3009/2019/2.1168 View / Download Pdf 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.
DOI: 10.29245/2578-3009/2019/2.1170 View / Download Pdf The Biochemical Fundamental Biomarkers of The Status of Health Against Cancer and Cardiovascular Diseases: Presence of Cortisol and Melatonin Circadian Rhythms, Normal Blood Levels of Fatty Acid Amide Hydrolase (FAAH) and Transforming Growth Factor-Beta (TGF-Beta), and Normal Values of Lymphocyte-to-Monocyte Ratio (LMR) and Atrial Natriuretic Peptide (ANP)-to-Endothelin-1 (Et-1) Ratio
Paolo Lissoni*, Giusy Messina, Franco Rovelli, Nicoletta Merli, Rosa Cusmai, Fernando Brivio, Arianna Lissoni, Giuseppe Di Fede
Institute of Biological Medicine, Milan, Italy
The future of laboratory analyses would require the identification of clinical parameters involving the main integrative biological functions including neuroendocrine, immune and cardiovascular systems, and capable of predicting the evidence of metabolic alterations and the possible occurrence of systemic diseases. According to the clinical data available up to now, the status of health may be identified by the following five major biomarkers, consisting of normal circadian rhythm of cortisol and the pineal hormone melatonin, normal blood concentrations of fatty acid amide hydrolase (FAAH), whose increase is associated with an endocannabinoid system deficiency, normal lymphocyte-to-monocyte ratio (LMR) values, normal blood levels of TGF-beta, the main immunosuppressive anti-inflammatory endogenous molecule, and normal values of ANP-to-ET-1 ratio. Since the evidence of alterations involving these five parameters may predispose to the onset of more severe metabolic disorders or systemic disease, the clinical evaluation of these five biomarkers could constitute the routinary laboratory analyses for realizing a real Preventive Medicine.
DOI: 10.29245/2578-3009/2019/3.1169 View / Download PdfValidation of the Comprehensive Arm Prosthesis and Rehabilitation Outcomes Questionnaire
Kerstin S. Baun1, Nathan T. Kearns2, Jennifer K. Peterson1, John M. Miguelez1
1Clinical Services, Advanced Arm Dynamics, Redondo Beach, CA, USA
2Department of Psychology, University of North Texas, Denton, TX, USA
Abstract
Purpose:
To develop and psychometrically evaluate the Comprehensive Arm Prosthesis and Rehabilitation Outcomes Questionnaire (CAPROQ), a 28-item, self-report measure of three key facets associated with successful rehabilitation (perceived function, satisfaction, and pain) designed specifically for the adult upper limb loss (ULL) population.
Materials and Methods:
Using a national sample of adult ULL patients (N=240), factor structure, internal consistency, convergent/concurrent validity, and known group validity of the total CAPROQ score and three subscale scores were evaluated.
Results:
Confirmatory factor analysis indicated adequate-to-strong factor loading on each subscale: satisfaction (.623-.913), perceived function (.572-.860) and pain (.422-.834). Internal consistencies for the total measure and measure subscales were good-to-excellent (.89-.95) and convergent validity indicated moderate-to-strong statistically significant associations between the CAPROQ subscales and relevant measures. Concurrent validity showed moderate associations between CAPROQ total score, prosthetic wear time, and psychosocial adjustment scores. Known group validity indicated significant differences on CAPROQ total score between initial and definitive fitting stages (p=.012).
Conclusion:
Psychometric evaluation indicated that the CAPROQ and CAPROQ subscales were structurally sound, internally consistent, and demonstrated convergent validity with currently used assessments of perceived functioning, satisfaction, and pain. CAPROQ is needed for guiding individual patient care, improving care models and future prosthesis selection and development.
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