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Background: Initial recurrence mapping of resected pancreatic ductal adenocarcinoma (PDAC) could help in stratifying patient subpopulations for optimal postoperative follow-up. The aim of this systematic review and meta-analysis was to investigate the initial recurrence patterns of PDAC and to correlate them with clinicopathological factors.Methods: MEDLINE and Web of Science databases were searched systematically for studies reporting first recurrence patterns after PDAC resection. Data were extracted from the studies selected for inclusion. Pooled odds ratios (ORs) and 95 per cent confidence intervals were calculated to determine the clinicopathological factors related to the recurrence sites. The weighted average of median overall survival was calculated.Results: Eighty-nine studies with 17 313 patients undergoing PDAC resection were included. The weighted median rates of initial recurrence were 20⋅8 per cent for locoregional sites, 26⋅5 per cent for liver, 11⋅4 per cent for lung and 13⋅5 per cent for peritoneal dissemination. The weighted median overall survival times were 19⋅8 months for locoregional recurrence, 15⋅0 months for liver recurrence, 30⋅4 months for lung recurrence and 14⋅1 months for peritoneal dissemination. Meta-analysis revealed that R1 (direct) resection (OR 2⋅21, 95 per cent c.i. 1⋅12 to 4⋅35), perineural invasion (OR 5⋅19, 2⋅79 to 9⋅64) and positive peritoneal lavage cytology (OR 5⋅29, 3⋅03 to 9⋅25) were significantly associated with peritoneal dissemination as initial recurrence site. Low grade of tumour differentiation was significantly associated with liver recurrence (OR 4⋅15, 1⋅71 to 10⋅07).

CDK4/6 inhibitors are approved to treat breast cancer and are in trials for other malignancies.We examined CDK4/6 inhibition in mouse and human CD8 T cells during early stages of activation. Mice receiving tumor-specific CD8 T cells treated with CDK4/6 inhibitors displayed increased T cell persistence and immunologic memory. CDK4/6 inhibition upregulated Mxd4, a negative regulator of Myc, in both mouse and human CD8 T cells. Silencing of Mxd4 or Myc in mouse CD8 T cells demonstrated the importance of this axis for memory formation. We used single cell transcriptional profiling and TCR clonotype tracking to evaluate recently activated human CD8 T cells in breast cancer patients before and during treatment with either palbociclib or abemaciclib. CDK4/6 inhibitor therapy in humans increases the frequency of CD8 memory precursors and downregulates their expression of MYC target genes, suggesting that CDK4/6 inhibitors in cancer patients may augment long-term protective immunity.

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