The impact of treatment factors on local control in T2-T3 anal carcinomas treated by radiotherapy with or without chemotherapy

Abstract

BACKGROUND This study was conducted to investigate the influence of therapeutic parameters on local control (LC) in the sphincter‐conserving treatment of T2‐T3 anal carcinoma. METHODS From 1976 to 1993, 137 patients with anal carcinoma classified as T2 (85 patients) or T3 (52 patients) were treated curatively by radiotherapy (RT) alone (54 patients) or by concomitant chemotherapy and RT (83 patients). RT was delivered in two sequences, with a median gap of 46 days between the sequences. The first sequence was delivered at a median dose of 39.6 gray (Gy) using megavoltage photon beams. Boost treatment consisted of either 192Ir implantation or external beam RT (median dose, 20 Gy). Chemotherapy started on Day 1 and generally consisted of 1 cycle of mitomycin C (10 mg/m2) and a 5‐day infusion of 5‐fluorouracil (600‐800 mg/m2/day). For surviving patients, median follow‐up was 83 months. Univariate and multivariate analyses were performed to determine therapeutic parameters affecting LC after adjustment for clinical factors. RESULTS The 5‐year actuarial LC was 76%. Factors associated with poorer LC (univariate) were as follows: age < 66 years (LC was 67% with the factor vs. 85% without), male gender (65% vs. 81%), tumor extent > 1/3 canal circumference (67% vs. 90%), lymph node involvement (64% vs. 81%), use of external beam boost (62% vs. 79%), and overall treatment time (OTT) ≥ 75 days (69% vs. 85%). In multivariate analysis, no therapeutic parameters remained significant when adjusted for significant clinical factors, although OTT was of borderline significance (P = 0.09). CONCLUSIONS The results of this multivariate analysis suggest that therapeutic factors have a less marked effect on LC compared with clinical parameters; the only factor that appeared to have some effect was OTT. Efforts to improve LC in patients with poor prognoses should concentrate on optimizing OTT and the chemotherapeutic aspects of treatment (in other words, attempts should be made to provide more effective agents and optimize scheduling). Cancer 1997; 79:2329‐35. © 1997 American Cancer Society.

Cyclin D1, cyclin E, and p21 have no apparent prognostic value in anal carcinomas treated by radiotherapy with or without chemotherapy

“…For completeness, the expression of p53 and Mib-1 was also included in our evaluation of cell-cycle-related factors, although these factors have been discussed in prior reports (Allal et al, 1997(Allal et al, , 1998(Allal et al, , 2002. Previous investigations of the prognostic value of cyclin E levels by using immunohistochemical techniques have produced conflicting results, for example, in breast cancer (Porter et al, 1997;Donnellan et al, 2001) and lung cancer (Anton et al, 2000;Muller-Tidow et al, 2001).…”

“…In all patients, treatment was delivered with curative intent at the University Hospital of Geneva, according to schedules whose details have previously been published (Allal et al, 1997). RT was delivered in a split course, the first sequence consisting of widefield external-beam RT (EBRT,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) and the second of a small-volume boost (EBRT or brachytherapy, 20 -22 Gy).…”

“…In anal carcinomas, indicators of patient outcome have traditionally been derived from clinical features, including tumour size/ stage, extent of lymph node involvement, and anatomical subsite (Cummings et al, 1991;Touboul et al, 1994;Allal et al, 1997). However, despite careful evaluation of these factors, it is not possible to reliably predict the outcome in individual patients.…”

Apparent lack of prognostic value of MIB-1 index in anal carcinomas treated by radiotherapy

“…Secondly, the present study is based on a subset of a larger series of patients treated during the same time period, with a correspondingly small number of events forming the basis for the analysis. However, the selection of patients for this study was biased only by the availability of adequate paraffin blocks, and the characteristics and clinical outcome of these patients were essentially identical to those of patients in the larger series (Allal et al, 1997). Nonetheless, even taking those remarks into consideration, our results suggest that the Mib-1 index is of little prognostic value, particularly considering the fact that the median values in patients with and without failure are essentially identical (52% vs 54%).…”

“…Correlation between Mib-1 index and clinicopathological parameters Because some clinical factors have been reported to be of prognostic value (Salmon et al, 1986;Goldman et al, 1987;Touboul et al, 1994;Allal et al, 1997), correlations of these parameters with Mib-1 indices were studied to assess potential linkage. In addition, a univariate analysis of the present series was undertaken to determine which clinical or therapeutic factors were significantly associated with a decrease in locoregional control.…”