RESUMO
Backgrounds/Aims: This study aimed to investigate patterns and factors affecting recurrence after curative resection for pancreatic ductal adenocarcinoma (PDAC). Methods: Consecutive patients who underwent curative resection for PDAC (2011-21) and consented to data and tissue collection (Barts Pancreas Tissue Bank) were followed up until May 2023. Clinico-pathological variables were analysed using Cox proportional hazards model. Results: Of 91 people (42 males [46%]; median age, 71 years [range, 43-86 years]) with a median follow-up of 51 months (95% confidence intervals [CIs], 40-61 months), the recurrence rate was 72.5% (n = 66; 12 loco-regional alone, 11 liver alone, 5 lung alone, 3 peritoneal alone, 29 simultaneous loco-regional and distant metastases, and 6 multi-focal distant metastases at first recurrence diagnosis). The median time to recurrence was 8.5 months (95% CI, 6.6-10.5 months). Median survival after recurrence was 5.8 months (95% CI, 4.2-7.3 months). Stratification by recurrence location revealed significant differences in time to recurrence between loco-regional only recurrence (median, 13.6 months; 95% CI, 11.7-15.5 months) and simultaneous loco-regional with distant recurrence (median, 7.5 months; 95% CI, 4.6-10.4 months; p = 0.02, pairwise log-rank test). Significant predictors for recurrence were systemic inflammation index (SII) ≥ 500 (hazard ratio [HR], 4.5; 95% CI, 1.4-14.3), lymph node ratio ≥ 0.33 (HR, 2.8; 95% CI, 1.4-5.8), and adjuvant chemotherapy (HR, 0.4; 95% CI, 0.2-0.7). Conclusions: Timing to loco-regional only recurrence was significantly longer than simultaneous loco-regional with distant recurrence. Significant predictors for recurrence were SII, lymph node ration, and adjuvant chemotherapy.
RESUMO
We have profiled, for the first time, an evolving human metastatic microenvironment by measuring gene expression, matrisome proteomics, cytokine and chemokine levels, cellularity, extracellular matrix organization, and biomechanical properties, all on the same sample. Using biopsies of high-grade serous ovarian cancer metastases that ranged from minimal to extensive disease, we show how nonmalignant cell densities and cytokine networks evolve with disease progression. Multivariate integration of the different components allowed us to define, for the first time, gene and protein profiles that predict extent of disease and tissue stiffness, while also revealing the complexity and dynamic nature of matrisome remodeling during development of metastases. Although we studied a single metastatic site from one human malignancy, a pattern of expression of 22 matrisome genes distinguished patients with a shorter overall survival in ovarian and 12 other primary solid cancers, suggesting that there may be a common matrix response to human cancer.Significance: Conducting multilevel analysis with data integration on biopsies with a range of disease involvement identifies important features of the evolving tumor microenvironment. The data suggest that despite the large spectrum of genomic alterations, some human malignancies may have a common and potentially targetable matrix response that influences the course of disease. Cancer Discov; 8(3); 304-19. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 253.