Pathomorphosis of Rectal Cancer Induced by Neoadjuvant Chemoradiotheraphy
Keywords:rectal cancer, preoperative radiotherapy, endolymphatic chemotherapy, pathomorphosis of rectal cancer
Purpose of the work was to develop and introduce in clinical practice new method of neoadjuvant chemoradiotherapy based on a combination of short course radiotherapy and endolymphatic chemotherapy and evaluate its effectiveness on the basis of therapeutic pathomorphosis.
Materials and methods. In the Donetsk regional anticancer center a method of combined neoadjuvant treatment of resectable rectal cancer has been developed, it’s consists of short course radiotherapy combined with endolymphatic chemotherapy 5-fluorouracil and followed surgical treatment within 48 hours. In 24 hours before starting radiotherapy the catheterization of lymphatic vessel on the thigh is performing. Infusion of 5-FU starting in 24 hours before the start of radiotherapy and subsequently carried out daily for 5 days, a single day dose usually does not exceed 1 g, total dose 5 g. For the purpose of modulation of the 5-FU chemotherapy effect intravenous introduction of calcium folinate was carried at the dosage of 50 mg daily for five days. Radiation therapy was performed by movable daily irradiation single local dose of 5 Gy to a total dose of 25 Gy. Surgery was performed within 48 hours after the end of neoadjuvant therapy.
The study group consisted of 64 patients who received short course of radiotherapy against the background of endolimfatic chemotherapy (group SCRT + E/L CT). The first control group consisted of 63 patients who received standard preoperative neoadjuvant short course of radiotherapy against the background intravenous chemotherapy (group SCRT + I/V CT). In the second control group consisted of 91 patients who received preoperative short course of radiotherapy (group SCRT).
Results and discussion. After using of short course radiotherapy supplemented by endolimfatic chemotherapy in tumor complexes clearly seen necrobiotic changes that lead to a total loss some of cells. As a result, in the lumen of tumor glands accumulated necrotic structureless mass. Dying tumor complexes surrounded by the apparent inflammatory cell infiltrate. Tumor cells in the complexes sharp dystrophic, gain ugly form. The boundaries between tumor cells erased. In some areas of the stroma located sharply dystrophic scattered tumor cells, that have lost the ability to form complexes. The wall of the large arterial vessels thickened, sclerosed. In veins and venules marked paretic dilatation lumen, in the arterioles — plasmatic impregnation. The lymphohistiocytic perivascular infiltration is observed. After analysis of morphometric parameters after neoadjuvant therapy noted that in the study group, where patients received SCRT + E/L CT alterative changes more apparent — 21.9 ± 5.1 %, than in the control groups, where patients received SCRT + I/V CT and SCRT, where the figures were 12.7 ± 4.2 % and 5.5 ± 2.4 % respectively (p = 0.012). In the study group the III degree of therapeutic pathomorphosis was prevailed versus I–II in the control groups that received SCRT + I/V CT and SCRT.
The use of preoperative short course of radiotherapy against the background of endolimfatic chemotherapy increased the 5-year overall survival up to 73.5 ± 6.3 % compared to control groups that received SCRT + I/V CT and SCRT, where the 5-year overall survival was 64.6 ± 5.8 % and 64.4 ± 6.8 % respectively (p < 0.05). The frequency of local recurrence rate in the study group was observed in 6.3 %, and the frequency of distant metastases was 15.6 %. In the control groups, that received SCRT + I/V CT and SCRT local recurrence tacked place in 9.9 and 11.1 % patients, the frequency of distant metastasis was 22.2 and 22.0 % respectively.
Conclusions. The results of pathological changes in the tumor tissue under the influence of neoadjuvant chemoradiotherapy completely correlated with clinical effectiveness characteristics, provided an objective appraisal of the direct effect of the treatment and shows the advantage of short course radiotherapy combined by endolymphatic chemotherapy compared with the control groups, which are received short course of radiotherapy against the background intravenous chemotherapy and short course of radiotherapy only.
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