Association between PD1 mRNA and response to anti-PD1 monotherapy across multiple cancer types.

Background: We hypothesized that the abundance of PD1 mRNA in tumor samples might explain the differences in overall response rates (ORR) observed following anti-PD1 monotherapy across cancer types. Patients and methods: RNASeqv2 data from 10 078 tumor samples representing 34 different cancer types was analyzed from TCGA. Eighteen immune-related gene signatures and 547 immune-related genes, including PD1, were explored. Correlations between each gene/signature and ORRs reported in the literature following anti-PD1 monotherapy were calculated. To translate the in silico findings to the clinical setting, we analyzed the expression of PD1 mRNA using the nCounter platform in 773 formalin-fixed paraffin embedded (FFPE) tumor samples across 17 cancer types. To test the direct relationship between PD1 mRNA, PDL1 immunohistochemistry (IHC), stromal tumor-infiltrating lymphocytes (sTILs) and ORR, we evaluated an independent FFPE-based dataset of 117 patients with advanced disease treated with anti-PD1 monotherapy. Results: In pan-cancer TCGA, PD1 mRNA expression was found strongly correlated (r > 0.80) with CD8 T-cell genes and signatures and the proportion of PD1 mRNA-high tumors (80th percentile) within a given cancer type was variable (0%-84%). Strikingly, the PD1-high proportions across cancer types were found strongly correlated (r = 0.91) with the ORR following anti-PD1 monotherapy reported in the literature. Lower correlations were found with other immune-related genes/signatures, including PDL1. Using the same population-based cutoff (80th percentile), similar proportions of PD1-high disease in a given cancer type were identified in our in-house 773 tumor dataset as compared with TCGA. Finally, the pre-established PD1 mRNA FFPE-based cutoff was found significantly associated with anti-PD1 response in 117 patients with advanced disease (PD1-high 51.5%, PD1-intermediate 26.6% and PD1-low 15.0%; odds ratio between PD1-high and PD1-intermediate/low = 8.31; P < 0.001). In this same dataset, PDL1 tumor expression by IHC or percentage of sTILs was not found associated with response. Conclusions: Our study provides a clinically applicable assay that links PD1 mRNA abundance, activated CD8 T-cells and anti-PD1 efficacy.

Home management of acute medical complications in cancer patients: a prospective pilot study.

BACKGROUND: The development of reliable alternatives to conventional hospitalization in patients with cancer would have great clinical and economical value. The aim of the present study was to assess the feasibility of a home-based nursing intervention model as a safe alternative for the management of acute medical complications in cancer patients who would otherwise require conventional hospitalization. PATIENTS AND METHODS: From October 2013 to October 2014, we prospectively evaluated the outcomes of consecutive acute medical episodes treated at home under the home-based intervention program named the Bridge Project (BP). Episodes were classified as "avoided hospitalization in outpatients" (AHO) vs. "reduced hospitalization in inpatients" (RHI). The primary end-point was to assess the rate and causes of BP intervention failure (unplanned hospital readmission or death). RESULTS: Two hundred and forty-six consecutive episodes (52 % AHO and 48 % RHI) involving 203 patients (55 % male; mean age 63 years) were enrolled. The main conditions managed at home were non-neutropenic infections (40 %), febrile neutropenia (20 %), and cancer-related complications (28 %). The median duration of the BP intervention was 5 days (range 1-16 days). No deaths were reported at home. Unplanned hospital readmissions occurred in 9 % of episodes (14 % in AHO vs. 4 % in RHI; p = 0.001). Five of the 22 readmitted patients (22.7 % of the BP failures; 2.5 % of the whole series) died during hospitalization. The BP intervention burden was 1353 days, representing a potential saving of 14 % of days of hospitalization during the study period. CONCLUSIONS: The BP is a safe intervention which can potentially avoid or reduce the length of hospitalization in selected cancer patients with acute medical complications. Our findings support further development of innovative home-based clinical approaches to promote potentially avoidable hospitalization in this setting.

Aetiology of community-acquired pneumonia among adults in an H1N1 pandemic year: the role of respiratory viruses.

This study aimed to determine the aetiology of community-acquired pneumonia (CAP) by adding polymerase chain reaction (PCR) to conventional methods and to describe the clinical and laboratory features between patients with bacterial pneumonia (BP) and viral pneumonia (VP). Adults with CAP admitted from November 2009 to October 2010 were included. Demographics, comorbidities, severity and clinical features were recorded. Conventional microbiological methods included blood and sputum cultures, acute and convalescent serologic samples, and antigen urinary detection. New methods included multiplex PCR for Mycoplasma pneumoniae, Legionella pneumophila, Chlamydophila pneumoniae, Bordetella pertussis and 15 respiratory viruses. A total of 169 patients were included. Using conventional methods, we identified a pathogen in 51 % of cases. With PCR, up to 70 % of cases had an aetiological diagnosis. Forty-five patients had BP (34 %), 22 had VP (17 %) and 25 (19 %) had co-infection (BP and VP). Pneumococci and respiratory syncytial virus (RSV) were the most frequently identified pathogens. Procalcitonin (PCT) and C-reactive protein (CRP) median values were significantly higher in BP than in VP patients. Shaking chills, higher CURB score and shock were significantly more frequent in BP. A viral infection was identified in more than one-third of patients with CAP. Clinical and laboratory features could help to differentiate between VP and BP and to guide empirical therapy.