title: Effect of long interval between hyperthermochemoradiation therapy and surgery for rectal cancer on apoptosis, proliferation and tumor response.
abstract: Neoadjuvant chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer, with surgery performed after an interval of a number of weeks. We have been conducting a clinical trial of preoperative chemoradiotherapy in combination with regional hyperthermia (hyperthermo-chemoradiation therapy; HCRT) for locally advanced rectal cancer. In the current study we assessed the effect of a longer (>10 weeks) interval after neoadjuvant HCRT on pathological response, oncological outcome and especially on apoptosis, proliferation and p53 expression in patients with rectal cancer. Forty-eight patients with proven rectal adenocarcinoma who underwent HCRT followed by surgery were identified for inclusion in this study. Patients were divided into two groups according to the interval between HCRT and surgery, ≤ 10 weeks (short-interval group) and >10 weeks (long-interval group). Patients in the long-interval group had a significantly higher rate of pathological complete response (pCR) (43.5% vs. 16.0%) than patients of the short-interval group. Patients of the long-interval group had a significantly higher rate of down-staging of T-stage (78.3% vs. 36.0%) and relatively higher rate of that of N-stage (52.2% vs. 36.0%) than patients of the short-interval group. Furthermore, apoptosis in the long-interval group was relatively higher compared to that of the short-interval group, without a significant difference in the Ki-67 proliferative index and expression of p53 in the primary tumor. In conclusion, we demonstrated that a longer interval after HCRT (>10 weeks) seemed to result in a better chance of a pCR, a result confirmed by the trends in tumor response markers, including apoptosis, proliferation and p53 expression.
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan Department of Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan taka.jifu@gmail.com.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Munenori
authors.initials: M
authors.lastname: Ide
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Takada
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Toshinaga
authors.initials: T
authors.lastname: Sutoh
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Morita
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Reina
authors.initials: R
authors.lastname: Yajima
authors.affiliation: Department of Surgical Oncology, Dokkyo Medical University, Mibu, Tochigi, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Soichi
authors.initials: S
authors.lastname: Tsutsumi
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asao
authors.affiliation: Department of Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Tetsunari
authors.initials: T
authors.lastname: Oyama
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D049109:Cell Proliferation; D059248:Chemoradiotherapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D006979:Hyperthermia, Induced; D007124:Immunoenzyme Techniques; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D002955:Leucovorin; D005472:Fluorouracil
keywords: HCRT; Rectal cancer; hyperthermochemoradiation therapy; tumor response