title: Individual tumor volume responses to short-course oxaliplatin-containing induction chemotherapy in locally advanced rectal cancer - Targeting the tumor for radiation sensitivity?
abstract: Neoadjuvant treatment of locally advanced rectal cancer (LARC) involves chemoradiotherapy (CRT), which may cause significant toxicity, and the potential role and sequential placement of neoadjuvant chemotherapy (NACT) relative to CRT is under debate.
  
  
  
  In a non-randomized study of 72 LARC patients, short-course oxaliplatin-containing NACT was administered prior to CRT. Tumor volumes were calculated from magnetic resonance images before and after NACT, and four weeks after CRT, and associations between tumor volume responses and outcome were analyzed. Additionally, the impact of oxaliplatin exposure on radiosensitivity was examined in colorectal carcinoma cell lines.
  
  
  
  All tumors except one responded to NACT, with better responses in T3 than T4 cases, and 69/72 patients obtained additional tumor volume reduction after subsequent CRT. However, no associations were found between tumor volume reduction and long-term outcome. Of note, oxaliplatin-resistant cells were significantly more radiosensitive than the oxaliplatin-sensitive counterparts.
  
  
  
  Oxaliplatin-containing NACT led to substantial tumor volume reduction with particularly good responses in T3 cases. NACT did not impede subsequent CRT response, and experimental results rather suggested enhanced radiosensitivity in oxaliplatin-exposed cells, encouraging studies to explore the administration of NACT prior to CRT. Data are still lacking to support omitting radiation in LARC management.
authors.affiliation: Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Norway; Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Norway. Electronic address: kjersti.flatmark@rr-research.no.
authors.forename: Kjersti
authors.initials: K
authors.lastname: Flatmark
authors.affiliation: Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Marie G
authors.initials: MG
authors.lastname: Saelen
authors.affiliation: Department of Radiology, Norwegian Radium Hospital, Oslo University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Knut H
authors.initials: KH
authors.lastname: Hole
authors.affiliation: Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Norway.
authors.forename: Torveig W
authors.initials: TW
authors.lastname: Abrahamsen
authors.affiliation: Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Karianne G
authors.initials: KG
authors.lastname: Fleten
authors.affiliation: Department of Oncology, Akershus University Hospital, Norway; Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Norway.
authors.forename: Helga H
authors.initials: HH
authors.lastname: Hektoen
authors.affiliation: Department of Oncology, Akershus University Hospital, Norway; Department of Radiation Biology, Norwegian Radium Hospital, Oslo University Hospital, Norway.
authors.forename: Kathrine R
authors.initials: KR
authors.lastname: Redalen
authors.affiliation: Department of Radiation Biology, Norwegian Radium Hospital, Oslo University Hospital, Norway; Department of Radiology, Norwegian Radium Hospital, Oslo University Hospital, Norway.
authors.forename: Therese
authors.initials: T
authors.lastname: Seierstad
authors.affiliation: Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Norway.
authors.forename: Svein
authors.initials: S
authors.lastname: Dueland
authors.affiliation: Department of Oncology, Akershus University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Anne H
authors.initials: AH
authors.lastname: Ree
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D011836:Radiation Tolerance; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D047368:Tumor Burden
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin
keywords: Chemoradiotherapy; Locally advanced rectal cancer; Neoadjuvant chemotherapy; Oxaliplatin