The first palliative care consultation to death interval has decreased over time at our center. Education is needed among our referring physicians for earlier access to palliative care. Prospective studies are needed to establish the appropriate timing of the first palliative care consultation.
Background
We sought to ascertain the immune effector function of pembrolizumab within the glioblastoma (GBM) microenvironment during the therapeutic window.
Methods
In an open-label, single-center, single-arm phase II “window-of-opportunity” trial in 15 patients with recurrent (operable) GBM receiving up to 2 pembrolizumab doses before surgery and every 3 weeks afterward until disease progression or unacceptable toxicities occurred, immune responses were evaluated within the tumor.
Results
No treatment-related deaths occurred. Overall median follow-up time was 50 months. Of 14 patients monitored, 10 had progressive disease, 3 had a partial response, and 1 had stable disease. Median progression-free survival (PFS) was 4.5 months (95% CI: 2.27, 6.83), and the 6-month PFS rate was 40%. Median overall survival (OS) was 20 months, with an estimated 1-year OS rate of 63%. GBM patients’ recurrent tumors contained few T cells that demonstrated a paucity of immune activation markers, but the tumor microenvironment was markedly enriched for CD68+ macrophages.
Conclusions
Immune analyses indicated that pembrolizumab anti–programmed cell death 1 (PD-1) monotherapy alone can’t induce effector immunologic response in most GBM patients, probably owing to a scarcity of T cells within the tumor microenvironment and a CD68+ macrophage preponderance.
8617 Background: Methadone (ME) is a highly effective opioid agonist used for difficult pain syndromes. However, the rotation from ME to another opioid may be difficult because of the absence of a uniformly accepted conversion ratio. Methods: We retrospectively reviewed consecutive medical records of Pts undergoing an opioid rotation from ME to an alternative opioid. For inclusion, Pts were required to have received ME for at least 3 days prior to the switch and reach a stable dose of the alternative opioid(s) during 7 days following. Stable dose was defined as a 30% or less change in opioid dose from one day to the next. For purposes of analysis, on the day before the switch, doses, were divided into ME doses and the oral morphine equivalent daily dose (MEDD), based on medication and route of all other opioids taken on that day, using standard equinalgesic tables. All doses after the switch were converted to the MEDD. For Pts receiving ME and a second opioid prior to the switch, the MEDD of the second opioid was subtracted from the MEDD calculated for the day when stable dose was reached. The remainder was used to calculate the equianalgesic raio with the previous ME dose. Results: Records on 39 Pts met inclusion criteria. Excluded from analysis were 5 Pts who were restarted on ME in < 8 days, 2 whose opioid dose markedly decreased of post switch, and 3 due to concerns about reliability of multiple routes used for fentanyl. Data from 29 Pts, 10 female, mean age 48 ±14.4 were evaluable. The ratio for: oral ME to MEDD was 1:4.7 (CL 3.0–6.5)(n=16), IV ME to MEDD was 1:13.5 (CL6.6–20.5)(n=13), p=0.06. ME dose is significantly correlated to stable MEDD after switching opioids for both ME IV and oral (Spearman=0.86,p=0.0001 and Spearman=0.72, p=0.0024, respectively. Mean day of achieving stable dose was on day 2.5 ±0.2 for IV ME and day 2.6±0.3 for oral ME. Conclusions: These dose ratios are new findings that will assist in switching Pts more safely to alternative opioids, when side effects or pain problems occur.An important difference in analgesic potency appears to exist between IV and oral ME. Further research with prospective studies is required. No significant financial relationships to disclose.
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