Background and Aim: The inhibition of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) has been a target for multiple drugs to enhance the T-cell antitumor activity. However, these immune checkpoint inhibitors (ICIs) come with a panel of immune-related adverse events (irAEs) that include mainly endocrine, skin, and gastrointestinal effects. We report seven cases of pancreatic irAEs in patients treated with ICIs at our institute. Methods: This is a case series; data was collected through chart review by 3 different data collectors and was analyzed separately by 2 physicians. Results: Of these seven cases, two had diabetic ketoacidosis (DKA), while five had pancreatitis diagnosed by a substantial rise in serum lipase. Pancreatitis was asymptomatic in two cases. A pancreatic biopsy in one case revealed type 2 autoimmune pancreatitis. The ICIs used included pembrolizumab, nivolumab, durvalumab, and avelumab. Treatment included steroids and holding the ICI therapy: three cases had complete resolution of pancreatitis while two cases required either a prolonged taper or a second course of prednisone for recurrence of pancreatitis. On the other hand, the DKA cases were treated with withdrawal of the ICI and starting insulin with no steroid therapy. Conclusions: Pancreatitis and DKA are rare adverse events of ICIs that can be controlled by holding the ICI with or without starting steroids. Rechallenging the patient with the same ICI is possible in selected cases.
e23557 Background: Leiomyosarcomas, are aggressive sarcomas with survival rates among the lowest of all soft tissue sarcomas. Patients with uterine leiomyosarcoma (ULMS) have worse overall survival (OS) than those with extra-uterine leiomyosarcoma (EULMS). The effect of several clinical factors on OS have been investigated, including age, tumor size, grade, stage, and use of chemotherapy. Looking at the epigenetics of the 2 diseases, differentially methylated regions (DMRs) were statistically significant between the 2 groups. Methods: The 2004-2016 National Cancer Database was queried for females with ULMS and EULMS. We investigated several factors as predictors of binary survival status (alive or dead): patient’s age, race, year at diagnosis, tumor grade, size and stage, receipt of surgical treatment, chemotherapy, palliative care, surgical margins and time to treatment in days. Univariate and backward stepwise multivariate logistic regression models were used to determine prognostic factors associated with survival in each group. Kaplan-Meier (KM) method with log-rank test was used to compare OS rates between the 2 groups. All analyses were conducted using Stata/SE 15.1. Results: The total number of subjects was 16883. The median OS was 36.7 months in ULMS vs 57.2 in EULMS (P < 0.001). Older age was associated with a lower likelihood of survival in both groups (OR = 0.95, P = 0.018 in ULMS; OR = 0.97, P < 0.001 in EULMS). Lymphovascular invasion and receipt of palliative care were associated with a relatively large decrease in survival in ULMS only (OR = 0.25, P < 0.001; OR = 0.13, P = 0.015 respectively). In the EULMS group, increased likelihood of survival was associated with later years of diagnosis (OR = 1.27; P < 0.001). Larger tumor size (OR = 0.39; P = 0.001), stages II-IV or unstageable disease (OR = 0.56; P < 0.001), positive surgical margins or margins that were unevaluable (OR = 0.87; P = 0.009) and receipt of systemic therapy (OR = 0.85; P = 0.016) were associated with a lower likelihood of survival. Conclusions: Our study reiterated that females with ULMS had worse OS than those with EULMS. this difference can be attributed to certain clinical risk factors, however, it may also be secondary to genetic and epigenetic factors. Surprisingly, the use of palliative care in this study was associated with poorer OS in the EULMS group. Further studies are needed to investigate the genetic map of these diseases and highlight certain potentially targetable prognostic and predictive factors. Study limitations: Our study did not stratify ULMS and EULMS according to the stage to examine if the aforementioned factors would still be relevant in the limited versus metastatic setting.
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