We thank Dr Velu and coauthors for their supportive comments. We acknowledge the preeminence of this group in understanding the predictive and prognostic impact of an inflammatory milieu in determining cancer outcomes in many settings. The work of Jamieson et al. (1) in operable patients was novel, and we are pleased to extend their findings to the metastatic setting.
We agree that the gold standard for such work involves the use of C-reactive protein and albumin. This unfortunately is not yet a routine test in clinical trials or indeed cancer therapy in clinical practice. Hence the neutrophil-lymphocyte ratio (NLR) and derived NLR, which have been shown to be a reasonable alternative measure (2–3), were chosen by us, as they were accessible in the largest number of patients. We are indeed pleased that their group has shown this to be an acceptable surrogate measure of an activated inflammatory milieu (2).
We also are intrigued by the prospect that this finding, regarding prognosis and the ability to identify a group with particularly poor outcomes, might also identify a group appropriate for novel interventions. This includes the phase II ruxolitinib data quoted, which is now the subject of a randomized phase III study. However, it may also uncover the potential for alternative targeted agents, including anti-angiogenesis agents, which could be revisited for this subgroup (4).
We agree that the recent understanding of the role of the host in determining outcomes in pancreatic cancer is highly significant, not only the inflammatory response but also those of critical stromal cells (5–7).
We look forward to novel treatment directions being tested, with both tumor and host factors influencing the choice of how to personalize therapy and improve results in this difficult-to-treat disease.
References
- 1. Jamieson NB, Glen P, McMillan DC, et al. Systemic inflammatory response predicts outcome in patients undergoing resection for ductal adenocarcinoma head of pancreas. Br J Cancer. 2005;92 (1):21–23. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Proctor MJ, McMillan DC, Morrison DS, Fletcher CD, Horgan PG, Clarke SJ. A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer. Br J Cancer. 2012;107 (4):695–699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Wang DS, Luo HY, Qiu MZ, et al. Comparison of the prognostic values of various inflammation based factors in patients with pancreatic cancer. Med Oncol. 2012;29 (5):3092–3100. [DOI] [PubMed] [Google Scholar]
- 4. Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 2014;15 (11):e493–e503. [DOI] [PubMed] [Google Scholar]
- 5. McCarroll JA, Naim S, Sharbeen G, et al. Role of pancreatic stellate cells in chemoresistance in pancreatic cancer. Front Physiol. 2014;5:141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Patel MB, Pothula SP, Xu Z, et al. The role of the hepatocyte growth factor/c-MET pathway in pancreatic stellate cell-endothelial cell interactions: anti-angiogenic implications in pancreatic cancer. Carcinogenesis. 2014;35 (8):1891–1900. [DOI] [PubMed] [Google Scholar]
- 7. Xu Z, Vonlaufen A, Phillips PA, et al. Role of pancreatic stellate cells in pancreatic cancer metastasis. J Pathol. 2010;177 (5):2585–2596. [DOI] [PMC free article] [PubMed] [Google Scholar]