High-grade acute organ toxicity during preoperative radiochemotherapy as positive predictor for complete histopathologic tumor regression in multimodal treatment of locally advanced rectal cancer.
OBJECTIVE
To test for a possible correlation between high-grade acute organ toxicity during preoperative radiochemotherapy and complete tumor regression after total mesorectal excision in multimodal treatment of locally advanced rectal cancer.


METHODS
From 2001 to 2008, 120 patients were treated. Preoperative treatment consisted of normofractionated radiotherapy at a total dose of 50.4 Gy, and either two cycles of 5-fluorouracil (5-FU) or two cycles of 5-FU and oxaliplatin. Toxicity during treatment was monitored weekly, and any toxicity CTC (Common Toxicity Criteria) >or= grade 2 of enteritis, proctitis or cystitis was assessed as high-grade organ toxicity for later analysis. Complete histopathologic tumor regression (TRG4) was defined as the absence of any viable tumor cells.


RESULTS
A significant coherency between high-grade acute organ toxicity and complete histopathologic tumor regression was found, which was independent of other factors like the preoperative chemotherapy schedule. The probability of patients with acute organ toxicity >or= grade 2 to achieve TRG4 after neoadjuvant treatment was more than three times higher than for patients without toxicity (odds ratio: 3.29, 95% confidence interval: [1.01, 10.96]).


CONCLUSIONS
Acute organ toxicity during preoperative radiochemotherapy in rectal cancer could be an early predictor of treatment response in terms of complete tumor regression. Its possible impact on local control and survival is under further prospective evaluation by the authors' working group.
Wolff
Hendrik Andreas
HA
Department of Radiotherapy and Radiooncology, University Medicine Göttingen, Göttingen, Germany.
Gaedcke
Jochen
J
Department of Surgery, University Medicine Göttingen, Göttingen, Germany.
Jung
Klaus
K
Department of Medical Statistics, University Medicine Göttingen, Göttingen, Germany.
Hermann
Robert Michael
RM
Department of Radiotherapy and Radiooncology, University Medicine Göttingen, Göttingen, Germany.|Department of Radiotherapy and Radiooncology, Ärztehaus am Diako, Bremen, Germany.
Rothe
Hilka
H
Department of Pathology, University Medicine Göttingen, Göttingen, Germany.
Schirmer
Markus
M
Department of Clinical Pharmacology, University Medicine Göttingen, Göttingen, Germany.
Liersch
Torsten
T
Department of Surgery, University Medicine Göttingen, Göttingen, Germany.
Herrmann
Markus Karl Alfred
MKA
Department of Radiotherapy and Radiooncology, University Medicine Göttingen, Göttingen, Germany.
Hennies
Steffen
S
Department of Radiotherapy and Radiooncology, University Medicine Göttingen, Göttingen, Germany.
Rave-Fränk
Margret
M
Department of Radiotherapy and Radiooncology, University Medicine Göttingen, Göttingen, Germany.
Hess
Clemens Friedrich
CF
Department of Radiotherapy and Radiooncology, University Medicine Göttingen, Göttingen, Germany.
Christiansen
Hans
H
Department of Radiotherapy and Radiooncology, University Medicine Göttingen, Göttingen, Germany. hchrist@gwdg.de.|Universitätsmedizin Göttingen, Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Robert-Koch-Str. 40, 37075, Göttingen, Germany. hchrist@gwdg.de.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003556:Cystitis / Q000209:etiology*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004751:Enteritis / Q000209:etiology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077150:Oxaliplatin; D011349:Proctitis / Q000209:etiology*; D011379:Prognosis; D011832:Radiation Injuries / Q000209:etiology*; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D013223:Statistics as Topic
D000964:Antimetabolites, Antineoplastic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil