Physician-reported reasons for non-enrollment of older adults in cancer clinical trials.

OBJECTIVES: Older adults (OA) are under-represented in cancer clinical trials. We sought to identify the proportion of OA(age > 65) vs. younger adults offered clinical trial and identify reasons patients were not offered a trial. METHODS: Consecutive patients with cancer (n = 503) seen by medical oncology in consultation were included. Oncologists provided reasons for not offering a study to patients who were offered and accepted systemic therapy. Comparison between older and younger adults was done using the Chi square test or Fisher exact test. Logistic regression was used to determine the association between age and being offered clinical trial participation. RESULTS: OA had worse performance status (PS) (ECOG 3+ 15.1% vs 5.2%, p < 0.0001) and more comorbidities (Charlson Comorbidity Index ≥2 24.7% vs 10.0%, p < 0.0001) than younger adults. OA were less likely to be offered systemic treatment (68.3% vs 82.1%, p < 0.001), but were as likely as younger adults to accept (86.6% vs 92.2%, p = 0.07). Of patients who accepted systemic treatment, 24.5% were offered trial enrollment. Taking into account patient factors and stage, increased age by decade was associated with a decreased likelihood of being offered a trial [OR 0.74 (95% CI 0.6-0.9), p < 0.001]. Reasons for not offering a trial included no available trial (75.4%), poor PS (7.8%) and ineligibility (6.3%). Poor PS (11.8% vs 3.9%) was more commonly cited for not offering a study to OA. CONCLUSIONS: Lack of clinical trials is the most common reason patients are not offered a trial. OA remain less likely to be offered a trial than younger adults.

Extended Synaptotagmin 1 Interacts with Herpes Simplex Virus 1 Glycoprotein M and Negatively Modulates Virus-Induced Membrane Fusion.

Enveloped viruses typically encode their own fusion machinery to enter cells. Herpesviruses are unusual, as they fuse with a number of cellular compartments throughout their life cycles. As uncontrolled fusion of the host membranes should be avoided in these events, tight regulation of the viral fusion machinery is critical. While studying herpes simplex virus 1 (HSV-1) glycoprotein gM, we identified the cellular protein E-Syt1 (extended synaptotagmin 1) as an interaction partner. The interaction took place in both infected and transfected cells, suggesting other viral proteins were not required for the interaction. Most interestingly, E-Syt1 is a member of the synaptotagmin family of membrane fusion regulators. However, the protein is known to promote the tethering of the endoplasmic reticulum (ER) to the plasma membrane. We now show that E-Syt1, along with the related E-Syt3, negatively modulates viral release into the extracellular milieu, cell-to-cell viral spread, and viral entry, all processes that implicate membrane fusion events. Similarly, these E-Syt proteins impacted the formation of virus-induced syncytia. Altogether, these findings hint at the modulation of the viral fusion machinery by the E-Syt family of proteins.IMPORTANCE Viruses typically encode their own fusion apparatus to enable them to enter cells. For many viruses, this means a single fusogenic protein. However, herpesviruses are large entities that express several accessory viral proteins to regulate their fusogenic activity. The present study hints at the additional participation of cellular proteins in this process, suggesting the host can also modulate viral fusion to some extent. Hence E-Syt proteins 1 and 3 seem to negatively modulate the different viral fusion events that take place during the HSV-1 life cycle. This could represent yet another innate immunity response to the virus.