Systemic release of osteoprotegerin during oxaliplatin-containing induction chemotherapy and favorable systemic outcome of sequential radiotherapy in rectal cancer
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Sebastian Meltzer1,3, Erta Kalanxhi1,2, Helga Helseth Hektoen1, Svein Dueland4, Kjersti Flatmark5,3,6, Kathrine Røe Redalen1, Anne Hansen Ree1,3
1Department of Oncology, Akershus University Hospital, Lørenskog, Norway
2Institute of Clinical Molecular Biology, Akershus University Hospital, Lørenskog, Norway
3Institute of Clinical Medicine, University of Oslo, Oslo, Norway
4Department of Oncology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway
5Department of Tumor Biology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway
6Department of Gastroenterological Surgery, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway
Anne Hansen Ree, e-mail: email@example.com
Keywords: osteoprotegerin, oxaliplatin, radiotherapy, metastasis, rectal cancer
Received: February 05, 2016 Accepted: April 10, 2016 Published: April 26, 2016
In colorectal cancer, immune effectors may be determinative for disease outcome. Following curatively intended combined-modality therapy in locally advanced rectal cancer metastatic disease still remains a dominant cause of failure. Here, we investigated whether circulating immune factors might correlate with outcome. An antibody array was applied to assay changes of approximately 500 proteins in serial serum samples collected from patients during oxaliplatin-containing induction chemotherapy and sequential chemoradiotherapy before final pelvic surgery. Array data was analyzed by the Significance Analysis of Microarrays software and indicated significant alterations in serum osteoprotegerin (TNFRSF11B) during the treatment course, which were confirmed by osteoprotegerin measures using a single-parameter immunoassay. Patients experiencing increase in circulating osteoprotegerin during the chemotherapy had significantly better 5-year progression-free survival than those without increase (78% versus 48%; P = 0.009 by log-rank test). Hence, systemic release of this soluble tumor necrosis factor decoy receptor following the induction phase of neoadjuvant therapy was associated with favorable long-term outcome in patients given curatively intended chemoradiotherapy and surgery but with metastatic disease as the main adverse event. This finding suggests that osteoprotegerin may mediate or reflect systemic anti-tumor immunity invoked by combined-modality therapy in locally advanced rectal cancer.
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