title: Systemic release of osteoprotegerin during oxaliplatin-containing induction chemotherapy and favorable systemic outcome of sequential radiotherapy in rectal cancer.
abstract: 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.
authors.affiliation: Department of Oncology, Akershus University Hospital, Lørenskog, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Meltzer
authors.affiliation: Department of Oncology, Akershus University Hospital, Lørenskog, Norway.|Institute of Clinical Molecular Biology, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Erta
authors.initials: E
authors.lastname: Kalanxhi
authors.affiliation: Department of Oncology, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Helga Helseth
authors.initials: HH
authors.lastname: Hektoen
authors.affiliation: Department of Oncology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Svein
authors.initials: S
authors.lastname: Dueland
authors.affiliation: Department of Tumor Biology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Gastroenterological Surgery, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Kjersti
authors.initials: K
authors.lastname: Flatmark
authors.affiliation: Department of Oncology, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Kathrine Røe
authors.initials: KR
authors.lastname: Redalen
authors.affiliation: Department of Oncology, Akershus University Hospital, Lørenskog, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Anne Hansen
authors.initials: AH
authors.lastname: Ree
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D059248:Chemoradiotherapy / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D008297:Male; D020360:Neoadjuvant Therapy / Q000379:methods*; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D053244:Osteoprotegerin / Q000097:blood*; D000077150:Oxaliplatin; D012004:Rectal Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D053244:Osteoprotegerin; D000077150:Oxaliplatin
keywords: metastasis; osteoprotegerin; oxaliplatin; radiotherapy; rectal cancer