Immunotherapy has dramatically changed the cancer treatment landscape during the past decade, but very limited efficacy has been reported against pancreatic cancer. Several factors unique to pancreatic cancer may explain the resistance: the well-recognized suppressive elements in the tumor microenvironment, the functional and structural barrier imposed by the stroma components, T cell exhaustion, the choice of perhaps the wrong immune targets, and microbial factors including gut dysbiosis and the unexpected presence of tumor microbes. Furthermore, we discuss various strategies to overcome these barriers.Research.

Background There are little data available regarding pattern of first metastases in resected MM as well as the response of advanced MM to cytotoxic therapy. Patients and Methods A retrospective, single-institution cohort was assembled of all patients with advanced/unresectable MM between 1995 and 2012 who received systemic therapy with available imaging (N=81). Responses to first- and second-line systemic therapy were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The relationship between response, OS, and clinical covariates was investigated using Cox proportional hazards regression. Results Primary sites included anorectal (N=31, 38%), vulvovaginal (N=28, 35%), head and neck (N=21, 26%), and gallbladder (N=1, 1%) mucosa. Seven percent of patients first relapsed in the brain. Cytotoxic therapy represented 82% and 51% of first- and second-line regimens. Best response achieved in the first-line setting was similar for single-agent (10%; 95% CI: 1–32%) and combination alkylator therapy (8%; 95% CI: 2–21%). Median OS from 1st-line treatment was 10.3 months (95% CI 8.7–13.9 months). Patients with elevated LDH (HR 1.87, 95% CI: 1.10–3.19, p=0.020) and ECOG performance status 1–2 (HR 1.69, 95% CI: 1.05–2.72, p=0.030) had a higher risk of death, while patients with 12-week objective responses had a lower risk of death (HR: 0.12, 95% CI: 0.04–0.41, p<0.001). Conclusion Cytotoxic systemic therapy has modest activity in advanced/unresectable MM, belying its adjuvant benefit. Patients whose tumors have an objective response to therapy have a lower chance of death. Brain imaging should be considered in routine surveillance.

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Although simulation has made significant gains, no single modality can be identified definitively as superior. Wholesale abandonment of live tissue training is not warranted. We maintain that combined live tissue and simulation-based training add value and should be continued. Congressional mandates may accelerate simulation development and improve performance.

Background: The clinical utility of a blood-based biomarker in squamous cell carcinoma of the anus (SCCA) is unknown. We analyzed carcinoembryonic antigen (CEA), a commonly employed assay for patients with colorectal adenocarcinoma, as a serum biomarker for patients with biopsy-proven SCCA. Materials and Methods: Medical records from 219 patients with biopsy-proven SCCA at the University of Texas MD Anderson Cancer Center were reviewed under an IRB-approved protocol from 2013 to 2020 to assess for correlations between CEA levels and corresponding clinical and pathologic characteristics.Results: The mean CEA among subgroups by clinical status at the time of presentation to our institution was highest among those patients with metastatic SCCA to visceral organs (M-V, 20.7 ng/mL), however this finding was not statistically significant by ANOVA (p = .74). By clinical subgroup, the percentage of patients with an abnormally elevated CEA was highest in those patients with metastatic disease to lymph nodes (M-L, 41.2%) followed by recurrent/unresectable SCCA (36.8%), and metastatic SCCA to visceral organs (M-V, 35.2%), and was statistically significant between groups (Fisher's exact test p = .02). Using RECIST criteria for tumor progression and disease response, the mean change in CEA for patients with progression was an increase in 19 ng/mL, compared to a change of -7.3 ng/mL in those with disease response (p = .004). We likewise assessed whether CEA levels were associated with survival outcomes for all patients with metastatic SCCA, and found no correlation between CEA and likelihood for survival in a ROC analysis (multivariate, age-adjusted analysis for CEA cutoff of 8, HR = 1.01, 95% CI 0.52-1.96).Conclusions: Despite interesting patterns of abnormally high CEA in SCCA patients with advanced disease, and correlation of increased CEA with disease progression (and conversely decreased CEA with disease response), CEA is not associated with survival outcomes in SCCA, and is not a clinically relevant biomarker in this disease.