103 Radiotherapy with concomitant chemotherapy superior to radiotherapy alone in the treatment of locally advanced anal cancer: Results of a phase III randomized trial of the EORTC radiotherapy and gastrointestinal tract cooperative groups

210

I. J. Radiation

Oncology

0 Biology

0 Physics

Volume

36, Number

1, Supplement,

1996

103 RADIOTHERAPY WITH CONCOMITANT CHEMOTHERAPY SUPERIOR TO RADIOTHERAPY ALONE TREATMENT OF LOCALLY ADVANCED ANAL CANCER: RESULTS OF A PHASE III RANDOMIZED EORTC RADIOTHERAPY AND GASTROINTESTINAL TRACT COOPERATIVE GROUPS H. Bartelink, Radiotherapy

F. Roelofsen, J.F. Basset, F. Eschwege, and Gastrointestinal Tract Cooperative

IEuropean Organization for Research AMSTERDAM, The Netherlands. Purpose: reducing

Ph. Rougier, Groups’

and Treatment

of Cancer,

D. Peiffert,

M. van Glabbeke,

c/o The Netherlands

Cancer

M. Pierart,

Institute,

To investigate the potential gain of the concomitant use of radiotherapy and chemotherapy the need for colostomy, a randomized phase-111 trial was performed in patients with 1ocaIly

IN THE TRIAL OF THE

on behalf

of the EORTC

Plesmanlaan

121, 1066 CX

in improving local control advanced anal cancer.

and

Material and methods: In the period 1987-1994 110 patients were randomized between radiotherapy alone and a combination of radiotherapy and chemotherapy. The patients had tumors larger than 4 cm, or TM NOS. or Tr.2 Nt-3 anal cancer. Radiotherapy consisted of45Gygivenin5weeks,withadailydoseof1.8Gy.AfterareJtperiodof6weeLsaboostof15Gyor20Gywasgivenincaseof partial or complete response respectively. Chemotherapy was given during radiotherapy, 750 mglm2 daily as continous infusion on day l-5 and 29-33, a single dose of Mitomycin C 15 mg/mz was administered on day 1. Results: The addition of chemotherapy to radiotheraw has resulted in an increase in the complete remission rate from 54% to 80%, and from 83% to 94% if results are considered after surgical resections. This has led to a significant improvement in loco-regional control and colostomy free survival (P=O.B4, P=O.O03 resp.) both in favor of the combined modality treatment. No significant difference was found when severe side effects were considered. The survival rate remained similar in both treatment arms. Skin ulceration, nodal involvement and sex were the most important prognostic factors for both local control and survival. These remained significant after multivariate analysis. The improvement seen in local control by adding chemotherapy to radiotherapy remained also significant after adjusting for prognostic factors in the multivariate analysis. Conclusions: The concomitant need for colostomy in patients

use of radiotherapy and chemotherapy with locally advanced anal cancer.

resulted

in an improved

local control

rate and a reduction

in the

104 Overexpression Bonin

ASTRO RESEARCH FELLOWSHIP of ~53 Protein is Associated with Decreased Local Disease-Free Survival in Patients Chemoradiation for Anal Canal Cancer: A Report of RTOG 87-04

Treated

S.R.,l

E.R.1

Qian

1~ox Chase Cancer 3Radiation Oncology

C.,2

Russell

Center, Center,

A.&3

Coia

L.R.,l

Paris

K.J.,4

Flam

M.S.,5

Sauter

Philadelphia, PA; 2American College of Radiology, Philadelphia, Sacramento, CA; 4James Graham Brown Cancer Center, Louisville, 5Saint Agnes Cancer Center, Fresno, CA

with

PA; KY;

Background/Purpose: Despite the encouraging results of chemoradiation as primary management of carcinoma of the anal canal, between 20 and 30% of patients will develop a local recurrence. As yet, no adequate pre-treatment factor other than AJCC Stage has been identified which would ahow clinicians to identify a subgroup of patients at highest risk of local recurrence. Overexpression of ~53 nuclear protein has been associated with a poor prognosis in cervical carcinoma, a disease etiologically and histologically similar to anal cancer. This study examines the prognostic significance of ~53 overexpression in the pretreatment biopsies of patients treated with deftitive chemoradiation for epidermoid carcinoma of the anal canal on a phase III randomized intergroup study, RTGG 87-04. Materials and Methods: Formahn fixed, paraffin embedded blocks or unstained slides from the pretreatment biopsies of 80 patients were obtained from referring institutions. Ah patients were treated on a prospective, randomized trial comparing radiotherapy (intended dose: 45 Gy to 50.4 Gy), to the pelvis with concurrent 5-FU or concurrent 5-FU and Mitomycin-C. After exclusion of specimens in which epidemroid cancer could not be identified or in whom follow-up data was not available, 58 patients were included in the study. Biopsies were evaluated by the immunohistcchemical method with the polyclonalp53 antibody CM-l. Those tumors in which greater than 5% of the nuclei stained for the ~53 protein were scored as positive. A multivariate regression model was used to analyze ovemxpression of p53 in terms of overall survival, local disease-free survival and disease free survival in relation to AJCC stage, age, KPS, treatment, sex, histology and ~53 status. Results: ~53 protein was overexpressed in 46.6% (27/58) of the cases. Them was a significantly decreased local disease-free survival in those patients whose tumors overexpressed ~53 (64% vs. 88% at 4 yrs, p = 0.027 by the Cox proportional hazard model, see table). Only AJCC stage was mom predictive of local disease-free survival than tumor p53 status. Statistically significant differences were not seen for overall survival or disease-free survival.

Conclusions: These results suggest that overexpression of the p53 protein is associated with a decrease in local disease-free survival in patients managed with definitive chemoradiation for epidennoid carcinoma of the anal canal. It may be cliicahy useful to perform immunohistochemical analysis of tumor ~53 status prior to treatment. Exposure to the increased morbidity associated with mom aggressive chemoradiation may best be limited to those patients whose tumors overexpress ~53. The RTGG is presently examining the role of high dose radiotherapy in the combined modality treatment of anal cancer (RTGG 95-03). Data on ~53 status will be collected prospectively and included in the analysis of prognostic variables of patients enrolled on that protocol. This project was supported

by the ASTRO

Research Fellowship

Fund and an RTGG

research grant