No abstract

Background The n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may prevent a range of chronic conditions through anti-inflammatory actions. However, since clinical trials using these fatty acids for primary prevention are yet unavailable their putative role in disease prevention rests, in part, on evidence of anti-inflammatory actions in healthy individuals. Objective To investigate in a double-blind, placebo-controlled clinical trial whether supplementation with a moderate dose of EPA+DHA reduces common biomarkers of chronic, systemic inflammation in healthy individuals. Methods A total of 261 healthy individuals aged 30–54 years who were free of inflammatory conditions and consumed ≤300 mg/day EPA+DHA were included in the study. Participants were randomly assigned to 18 weeks of either fish oil supplementation providing 1400 mg/day EPA+DHA or matching placebo. Outcome measures were serum levels of C-reactive protein (CRP) and interleukin (IL)-6. In a substudy, ex vivo cytokine production was measured. Missing data for CRP and IL-6 were estimated using regression imputation. Data analyses conformed to intention-to-treat principles. Results Participant blinding was verified. Is the meaning of this sentence still correct? EPA+DHA levels increased by 64% in the active treatment group, but serum levels of CRP and IL-6 were not affected by supplementation (P ≥ 0.20). Findings were consistent with and without imputed values and across subgroups. Similarly, EPA+DHA supplementation did not alter ex vivo production of four pro-inflammatory cytokines (P ≥ 0.20). Conclusions Supplementation with 1400 mg EPA+DHA did not reduce common markers of systemic inflammation in healthy adults. Whether this or a higher dose affects other measures of inflammation, oxidative stress, or immune function warrants examination.

STK11 was first recognized as a tumor suppressor gene in the late 1990s based on linkage analysis of patients with Peutz‐Jeghers syndrome. STK11 encodes LKB1, an intracellular serine‐threonine kinase involved in cellular metabolism, cell polarization, regulation of apoptosis, and DNA damage response. Recurrent somatic loss‐of‐function mutations occur in multiple cancer types, most notably in 13% of lung adenocarcinomas. Recent reports indicate that KRAS‐mutant non‐small cell lung cancers harboring co‐mutations in STK11 do not respond to PD‐1 axis inhibitors. We present three patients with STK11‐mutated tumors and discuss the proposed mechanisms by which germline and somatic alterations in STK11 promote carcinogenesis, potential approaches for therapeutic targeting, and the new data on resistance to immune checkpoint inhibitors. Key Points STK11 is a tumor suppressor gene, and loss‐of‐function mutations are oncogenic, due at least in part to loss of AMPK regulation of mTOR and HIF‐1‐α. Clinical trials are under way, offering hope to patients whose STK11‐mutated tumors are refractory and/or have progressed on chemotherapeutic regimens. Whether gastrointestinal cancers with STK11 loss of function will show the same outcome and potential refractoriness to immune therapy that were reported for lung cancer is unknown. However, physicians managing such patients should consider the experience in lung cancer, particularly outside the context of a clinical trial. In the CheckMate‐057 trial lung tumors harboring co‐mutations in KRAS and STK11 had an inferior response to PD‐1 axis inhibitors. Coupled with the observation that STK11‐mutated tumors were found to have a cold immune microenvironment regardless of KRAS status, the conclusion could extend to KRAS wild‐type tumors with STK11 mutation. Current data suggest that the use of PD‐1 axis inhibitors may be ill advised in the presence of STK11 mutation.

No abstract

e14596 Background: Radiomics features, which are quantitative features generated by computational analysis of routine clinical imaging like CT scans, have been shown to be associated with clinical outcomes and tumor’s behavior in some solid tumors. We compared the radiomic features of malignant and benign pheochromocytomas/paragangliomas (P/P). Methods: Through an IRB approved study at our institution, we identified 20 consecutive patients with P/P and with available contrast-enhanced abdominopelvic CT. A radiologist with experience in oncologic imaging identified and segmented tumors on every slice using a MatLab-based imaging platform. The entire tumor image then underwent computational analysis generating 1160 radiomics features reflecting tumor size, shape, density, textural heterogeneity, and margins. These radiomics features were compared between malignant and benign P/P using Wilcoxon-Rank sum test. Results: Of the twenty patients included in this analysis, there were 6 patients with malignant P/P and 14 patients with benign tumors. Patients had been followed for at least 5 and many for at least 10 years after resection of the tumor. At diagnosis, the mean age of patients with benign and malignant tumors were 51 and 45, respectively. A 60% majority of patients with benign tumors were females while a 77% majority of patients with malignant tumors were male. Benign P/P were significantly different from malignant ones in: tumor intensity textures (spatial correlation [p-value = 0.0010], Laws [p-value = 0.0064], LoG [p-value = 0.0087], and Gabor [p-value = 0.0325]), and tumor local surface shape (Shape Index SI7 [p-value = 0.0325]). Conclusions: This initial analysis sought to discern differences in these rare tumors that might be exploited clinically. The results show that compared to benign tumors, malignant P/P tend to have more heterogenous texture, irregular edges, and less rounded shape on contrast enhanced abdominal CT scan. However, because these radiomics phenotype properties are subtle, they cannot be made reliably in an objective fashion using human visual assessment and thus these radiomics features may have a role as a quantitative imaging biomarker in P/P to predict tumor behavior. The cohort is being expanded and data will be updated at the time of the presentation. With larger numbers, the contribution to the radiomics profile of a SDHx mutation will be explored in greater depth to understand the differential impact of SDHx loss and of evolution into a cancer to the radiomics profiles.