High-grade acute organ toxicity as a positive prognostic factor in primary radiochemotherapy for anal carcinoma.
OBJECTIVE
To test for a possible correlation between high-grade acute organ toxicity during primary radiochemotherapy and treatment outcome for patients with anal carcinoma.


METHODS
From 1991 to 2009, 72 patients with anal carcinoma were treated at our department (10 patients had stage I, 28 patients had stage II, 11 patients had stage IIIA, and 13 patients had stage IIIB cancer [Union Internationale Contre le Cancer criteria]). All patients received normofractionated (1.8 Gy/day, five times/week) whole-pelvis irradiation including iliac and inguinal lymph nodes with a cumulative dose of 50.4 Gy. Concomitant chemotherapy regimen consisted of two cycles of 5-fluorouracil (1,000 mg/m(2)total body surface area (TBSA)/day as continuous intravenous infusion on days 1-4 and 29-32) and mitomycin C (10 mg/m(2)/TBSA, intravenously on days 1 and 29). Toxicity during treatment was monitored weekly, and any incidence of Common Toxicity Criteria (CTC) grade of ≥3 for skin reaction, cystitis, proctitis, or enteritis was assessed as high-grade acute organ toxicity for later analysis.


RESULTS
We found significant correlation between high-grade acute organ toxicity and overall survival, locoregional control, and stoma-free survival, which was independent in multivariate analysis from other possible prognostic factors: patients with a CTC acute organ toxicity grade of ≥3 had a 5-year overall survival rate of 97% compared to 30% in patients without (p < 0.01, multivariate analysis; 97% vs. 48%, p = 0.03 for locoregional control, and 95% vs. 59%, p = 0.05 for stoma-free survival).


CONCLUSIONS
Our data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, since high-grade acute organ toxicity during radiochemotherapy showed itself to be an independent prognostic marker in our patient population. This hypothesis should be further analyzed by using biomolecular and clinical levels in future clinical trials.
Wolff
Hendrik Andreas
HA
Department of Radiotherapy and Radiooncology, Universitätsmedizin Göttingen, Germany.
Raus
Ismene
I
Jung
Klaus
K
Schüler
Phillip
P
Herrmann
Markus Karl
MK
Hennies
Steffen
S
Vorwerk
Hilke
H
Hille
Andrea
A
Hess
Clemens Friedrich
CF
Christiansen
Hans
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D003556:Cystitis / Q000209:etiology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004751:Enteritis / Q000209:etiology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D015182:Lymphatic Irradiation / Q000009:adverse effects / Q000379:methods; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects; D009364:Neoplasm Recurrence, Local / Q000601:surgery; D009367:Neoplasm Staging; D011349:Proctitis / Q000209:etiology; D011379:Prognosis; D011855:Radiodermatitis / Q000209:etiology; D011879:Radiotherapy Dosage; D012074:Remission Induction / Q000379:methods; D016879:Salvage Therapy / Q000379:methods; D016896:Treatment Outcome
D016685:Mitomycin; D005472:Fluorouracil