Beyond Concurrent Chemoradiation: The Emerging Role of PD-1/PD-L1 Inhibitors in Stage III Lung Cancer.

Concurrent chemoradiation (cCRT) with platinum-based chemotherapy is standard-of-care therapy for patients with stage III unresectable non-small cell lung cancer (NSCLC). Although cCRT is potentially curative, 5-year overall survival has hovered around 20%, despite extensive efforts to improve outcomes with increasing doses of conformal radiation and intensification of systemic therapy with either induction or consolidation chemotherapy. PD-1/PD-L1 immune checkpoint inhibitors have demonstrated unprecedented efficacy in patients with stage IV NSCLC. In addition, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote antitumor immunity, which has led to the initiation of clinical trials testing these drugs in patients with stage III NSCLC. A preliminary report of a randomized phase III trial, the PACIFIC trial, demonstrated an impressive increase in median progression-free survival with consolidative durvalumab, a PD-L1 inhibitor, compared with observation after cCRT. Here, we discuss the clinical and translational implications of integrating PD-1/PD-L1 inhibitors in the management of patients with unresectable stage III NSCLC

MUSTANG 3.3 Millimeter Continuum Observations of Class 0 Protostars

We present observations of six Class 0 protostars at 3.3 mm (90 GHz) using the 64-pixel MUSTANG bolometer camera on the 100-m Green Bank Telescope. The 3.3 mm photometry is analyzed along with shorter wavelength observations to derive spectral indices (S_nu ~ nu^alpha) of the measured emission. We utilize previously published dust continuum radiative transfer models to estimate the characteristic dust temperature within the central beam of our observations. We present constraints on the millimeter dust opacity index, beta, between 0.862 mm, 1.25 mm, and 3.3 mm. Beta_mm typically ranges from 1.0 to 2.4 for Class 0 sources. The relative contributions from disk emission and envelope emission are estimated at 3.3 mm. L483 is found to have negligible disk emission at 3.3 mm while L1527 is dominated by disk emission within the central beam. The beta_mm^disk <= 0.8 - 1.4 for L1527 indicates that grain growth is likely occurring in the disk. The photometry presented in this paper may be combined with future interferometric observations of Class 0 envelopes and disks.Comment: 19 pages, 3 figures, AJ accepted, in pres

Observations of M87 and Hydra A at 90 GHz

This paper presents new observations of the AGNs M87 and Hydra A at 90 GHz made with the MUSTANG bolometer array on the Green Bank Telescope at 8.5" resolution. A spectral analysis is performed combining this new data and archival VLA data on these objects at longer wavelengths. This analysis can detect variations in spectral index and curvature expected from energy losses in the radiating particles. M87 shows only weak evidence for steepening of the spectrum along the jet suggesting either re-acceleration of the relativistic particles in the jet or insufficient losses to affect the spectrum at 90 GHz. The jets in Hydra A show strong steepening as they move from the nucleus suggesting unbalanced losses of the higher energy relativistic particles. The difference between these two sources may be accounted for by the different lengths over which the jets are observable, 2 kpc for M87 and 45 kpc for Hydra A.Comment: 11 pages, submitted to Ap

CMB observations with the Jodrell Bank - IAC interferometer at 33 GHz

The paper presents the first results obtained with the Jodrell Bank - IAC two-element 33 GHz interferometer. The instrument was designed to measure the level of the Cosmic Microwave Background (CMB) fluctuations at angular scales of 1 - 2 degrees. The observations analyzed here were taken in a strip of the sky at Dec = +41 deg with an element separation of 16.7 lambda, which gives a maximum sensitivity to ~1.6 deg structures on the sky. The data processing and calibration of the instrument are described. The sensitivity achieved in each of the two channels is 7 micro K per resolution element. A reconstruction of the sky at Dec = +41 deg using a maximum entropy method shows the presence of structure at a high level of significance. A likelihood analysis, assuming a flat CMB spatial power spectrum, gives a best estimate of the level of CMB fluctuations of Delta Tl = 43 (+13,-12) micro K for the range l = 109 +/- 19; the main uncertainty in this result arises from sample variance. We consider that the contamination from the Galaxy is small. These results represent a new determination of the CMB power spectrum on angular scales where previous results show a large scatter; our new results are in agreement with the theoretical predictions of the standard inflationary cold dark matter models.Comment: 11 pages, 11 figures. Web site at http://www.jb.man.ac.uk/research/cmb/ Accepted for publication in MNRA

The Radio - 2 mm Spectral Index of the Crab Nebula Measured with GISMO

We present results of 2 mm observations of the Crab Nebula, obtained using the Goddard-IRAM Superconducting 2 Millimeter Observer (GISMO) bolometer camera on the IRAM 30 m telescope. Additional 3.3 mm observations with the MUSTANG bolometer array on the Green Bank Telescope are also presented. The integrated 2 mm flux density of the Crab Nebula provides no evidence for the emergence of a second synchrotron component that has been proposed. It is consistent with the radio power law spectrum, extrapolated up to a break frequency of log(nu_{b} [GHz]) = 2.84 +/- 0.29 or nu_{b} = 695^{+651}_{-336} GHz. The Crab Nebula is well-resolved by the ~16.7" beam (FWHM) of GISMO. Comparison to radio data at comparable spatial resolution enables us to confirm significant spatial variation of the spectral index between 21 cm and 2 mm. The main effect is a spectral flattening in the inner region of the Crab Nebula, correlated with the toroidal structure at the center of the nebula that is prominent in the near-IR through X-ray regime.Comment: Accepted for publication in the Ap

Gene Expression Profiles as Markers of Aggressive Disease-EGFR as a Factor

We previously reported that 43 (58%) of 75 head and neck squamous cell carcinoma (HNSCC) tumors harbor increased epidermal growth factor receptor (EGFR) gene copy numbers as determined by fluorescent in situ hybridization. In this study, an increased EGFR copy number was associated with decreased progression-free survival and overall survival of HNSCC patients. However, activated EGFR protein levels are difficult to quantify by immunohistochemistry and are subject to dynamic regulation, specifically receptor downregulation on ligand binding. Therefore, we generated an activated EGFR gene expression signature in an in vitro HaCaT keratinocyte model system to further study genes involved in the EGFR signaling pathway in HNSCC. The results from this model system have suggested that the activated EGFR signature might reflect the activated state of the EGFR pathway in human HNSCC tumors and that it is associated with the increased EGFR gene copy number by fluorescent in situ hybridization. Furthermore, the activated EGFR signature has provided additional leads, because they are related to co-regulated molecular pathways and associated gene products on activation of EGFR. These could be exploited to refine and optimize combination therapies to be used in conjunction with available EGFR inhibitors in individual HNSCC patients

Implications of a High Angular Resolution Image of the Sunyaev-Zel'dovich Effect in RXJ1347-1145

The most X-ray luminous cluster known, RXJ1347-1145 (z=0.45), has been the object of extensive study across the electromagnetic spectrum. We have imaged the Sunyaev-Zel'dovich Effect (SZE) at 90 GHz (3.3 mm) in RXJ1347-1145 at 10" resolution with the 64-pixel MUSTANG bolometer array on the Green Bank Telescope (GBT), confirming a previously reported strong, localized enhancement of the SZE 20" to the South-East of the center of X-ray emission. This enhancement of the SZE has been interpreted as shock-heated (> 20 keV) gas caused by an ongoing major (low mass-ratio) merger event. Our data support this interpretation. We also detect a pronounced asymmetry in the projected cluster pressure profile, with the pressure just east of the cluster core ~1.6 times higher than just to the west. This is the highest resolution image of the SZE made to date.Comment: 9 pages, 7 figures; accepted for publication in The Astrophysical Journa