Expectant management of small asymptomatic, sporadic, NF-PNETs could be a reasonable option in highly selected patients. However, the level of evidence is low and longer follow-up is needed to identify patients could benefit from upfront surgery instead of expectant treatment.

Identifying hyperactive kinases in cancer is crucial for individualized treatment with specific inhibitors. Kinase activity can be discerned from global protein phosphorylation profiles obtained with mass spectrometry‐based phosphoproteomics. A major challenge is to relate such profiles to specific hyperactive kinases fueling growth/progression of individual tumors. Hitherto, the focus has been on phosphorylation of either kinases or their substrates. Here, we combined label‐free kinase‐centric and substrate‐centric information in an Integrative Inferred Kinase Activity ( INKA ) analysis. This multipronged, stringent analysis enables ranking of kinase activity and visualization of kinase–substrate networks in a single biological sample. To demonstrate utility, we analyzed (i) cancer cell lines with known oncogenes, (ii) cell lines in a differential setting (wild‐type versus mutant, +/− drug), (iii) pre‐ and on‐treatment tumor needle biopsies, (iv) cancer cell panel with available drug sensitivity data, and (v) patient‐derived tumor xenografts with INKA ‐guided drug selection and testing. These analyses show superior performance of INKA over its components and substrate‐based single‐sample tool KARP , and underscore target potential of high‐ranking kinases, encouraging further exploration of INKA 's functional and clinical value.

BackgroundDuodenal adenocarcinoma (DA) is a rare tumor for which survival data per treatment modality and disease stage are unclear. This systematic review and meta-analysis aims to summarize the current literature on patient outcome after surgical, (neo)adjuvant, and palliative treatment in patients with DA.MethodsA systematic search was performed according to the preferred reporting items for systematic reviews and meta-analyses guidelines, to 25 April 2017. Primary outcome was overall survival (OS), specified for treatment strategy or disease stage. Random-effects models were used for the calculation of pooled odds ratios per treatment modality. Included papers were also screened for prognostic factors.ResultsA total of 26 observational studies, comprising 6438 patients with DA, were included. Of these, resection with curative intent was performed in 71% (range 53–100%) of patients, and 29% received palliative treatment (range 0–61%). The pooled 5-year OS rate was 46% after curative resection, compared with 1% in palliative-treated patients (OR 0.04, 95% confidence interval [CI] 0.02–0.09, p < 0.0001). Both segmental resection and pancreaticoduodenectomy allowed adequate assessment of lymph node involvement and resulted in similar OS. Lymph node involvement correlated with worse OS (pooled 5-year survival rate 21% for nodal metastases vs. 65% for node-negative disease; OR 0.17, 95% CI 0.11–0.27, p < 0.0001). In the current literature, no survival benefit for adjuvant therapy after curative resection was found.ConclusionResection with curative intent, either pancreaticoduodenectomy or segmental resection, and lack of nodal metastases, favors survival for DA. Further studies exploring multimodality (neo)adjuvant therapy are warranted to investigate their benefit.Electronic supplementary materialThe online version of this article (10.1245/s10434-018-6567-6) contains supplementary material, which is available to authorized users.