Radiomodifiers in the combined treatment of rectal cancer patients

Abstract

Objective. To evaluate the effectiveness of the combined method of treatment of patients with rectal cancer using several variants of polyradiomodification (CT+PRM). Material and methods. To increase the effectiveness of the «short» course of neoadjuvant radiation therapy (RT) 5×5 Gy until total focal dose Gy, the concept of polyradiomodification proposed by S. P. Yarmonenko (1982) was used [1]. Three radiomodifiers were used: local intracavitary microwave hyperthermia (MWH), Metronidazole (MZ) as part of a polymer composition for intrarectal administration, and the chemotherapy drug Capecitabine (Cap). Four variants of the PRM have been created, divided into two-component and three-component. Two-component variants were used when the MWH was not possible in the case of stenosis or localization of cancer in the upper ampullary rectum. Initially, Capecitabine was used at a daily dose of 1.5 g/m2 on 1–5 days in combination with a double administration of Metronidazole («Cap5+MZ») and surgery 3 weeks after RT, and later the dose of Capecitabine was increased to 2.0 g/m2 on 1–14 days («Cap14+MZ») with surgery 4–6 weeks after RT. With three-component versions of PRM, 3 additional sessions of MWH were used: «Cap5+MZ+MWH» and «Cap14+MZ+MWH». A total of 241 patients were included in the study. Results. The total toxicity in CT+PRM was 33.4%, and the overall rate of postoperative complications was 14.9%. The 5-year relapse-free survival (RFS) rate of 80.5% was achieved due to pronounced local control: cancer recurrence was detected only in 1 (0.4%) of 241 patients. This made it possible to perform sphincter-sparing operations (SSO) without compromising oncological results in 211 (86.7%) patients out of 241. The most pronounced therapeutic pathomorphosis in the tumor was achieved with «Cap14+MZ» and «Cap14+MZ+MWH»: pathomorphosis of the III degree was achieved in 9 (30.0%) of 30 patients with «Cap14+MZ», and in 13 (25.0%) of 52 patients with «Cap14+MZ+MWH», a complete pathomorphological response was detected in 7 (23.4%) of 30 patients with «Cap14+MZ», and in 9 (17.3%) of 52 patients with «Cap14+MZ+MWH». When reaching the III–IV degree of pathomorphosis, distant metastases were detected in 6.3% of patients, at the II degree and below — in 19.7% (p=0.01). Conclusion. When using CT+PRM, 5-year RFS rate was increased to 80.5%, and the frequency of SSO was increased to 86.7%, with a low level of postoperative complications (14.9%) and acceptable toxicity (33.4%).