The value of post-operative chemotherapy after chemoradiotherapy in patients with high-risk locally advanced rectal cancer-results from the RAPIDO trial.

BACKGROUND: Pre-operative chemoradiotherapy (CRT) rather than radiotherapy (RT) has resulted in fewer locoregional recurrences (LRRs), but no decrease in distant metastasis (DM) rate for patients with locally advanced rectal cancer (LARC). In many countries, patients receive post-operative chemotherapy (pCT) to improve oncological outcomes. We investigated the value of pCT after pre-operative CRT in the RAPIDO trial. PATIENTS AND METHODS: Patients were randomised between experimental (short-course RT, chemotherapy and surgery) and standard-of-care treatment (CRT, surgery and pCT depending on hospital policy). In this substudy, we compared curatively resected patients from the standard-of-care group who received pCT (pCT+ group) with those who did not (pCT- group). Subsequently, patients from the pCT+ group who received at least 75% of the prescribed chemotherapy cycles (pCT ≥75% group) were compared with patients who did not receive pCT (pCT-/- group). By propensity score stratification (PSS), we adjusted for the following unbalanced confounders: age, clinical extramural vascular invasion, distance to the anal verge, ypT stage, ypN stage, residual tumour, serious adverse event (SAE) and/or readmission within 6 weeks after surgery and SAE related to pre-operative CRT. Cumulative probability of disease-free survival (DFS), DM, LRR and overall survival (OS) was analysed by Cox regression. RESULTS: In total, 396/452 patients had a curative resection. The number of patients in the pCT+, pCT >75%, pCT- and pCT-/- groups was 184, 112, 154 and 149, respectively. The PSS-adjusted analyses for all endpoints demonstrated hazard ratios between approximately 0.7 and 0.8 (pCT+ versus pCT-), and 0.5 and 0.8 (pCT ≥75% versus pCT-/-). However, all 95% confidence intervals included 1. CONCLUSIONS: These data suggest a benefit of pCT after pre-operative CRT for patients with high-risk LARC, with approximately 20%-25% improvement in DFS and OS and 20%-25% risk reductions in DM and LRR. Compliance with pCT additionally reduces or improves all endpoints by 10%-20%. However, differences are not statistically significant.

Electrochemotherapy: a new technological approach in treatment of metastases in the liver.

Electrochemotherapy is now in development for treatment of deep-seated tumors, like in bones and internal organs, such as liver. The technology is available with a newly developed electric pulse generator and long needle electrodes; however the procedures for the treatment are not standardized yet. In order to describe the treatment procedure, including treatment planning, within the ongoing clinical study, a case of successful treatment of a solitary metastasis in the liver of colorectal cancer is presented. The procedure was performed intraoperatively by inserting long needle electrodes, two in the center of the tumor and four around the tumor into the normal tissue. The insertion of electrodes proved to be feasible and was done according to the treatment plan, prepared by numerical modeling. After intravenous bolus injection of bleomycin the tumor was exposed to electric pulses. The delivery of the electric pulses did not interfere with functioning of the heart, since the pulses were synchronized with electrocardiogram in order to be delivered outside the vulnerable period of the ventricles. Also the post treatment period was uneventful without side effects. Re-operation of the treated metastasis demonstrated feasibility of the reoperation, without secondary effects of electrochemotherapy on normal tissue. Good antitumor effectiveness with complete tumor destruction was confirmed with histological analysis. The patient is disease-free 16 months after the procedure. In conclusion, treatment procedure for electrochemotherapy proved to be a feasible technological approach for treatment of liver metastasis. Due to the absence of the side effects and the first complete destruction of the treated tumor, treatment procedure for electrochemotherapy seems to be a safe method for treatment of liver metastases with good treatment effectiveness even in difficult-to-reach locations.

Immunohistochemical localization of group II phospholipase A2 in the tumours and mucosa of the colon and rectum.

BACKGROUND: Group II phospholipase A(2)(PLA(2)) is an enzyme important in malignant transformation and in the invasion process of malignant cells. The aim of the present study was to investigate the expression of group II PLA(2)in the cancers of the colorectum, peritumoural mucosa and in the mucosa distant from the tumour. METHODS: Resection specimens from 57 patients with colorectal carcinoma (caecum 10, ascending 10, transverse 10, sigmoid colon nine, and rectum 18) were analysed immunohistochemically. Histological slides from paraffin blocks were stained by the human monoclonal group II PLA(2)antibody ('Upstate Biotechnology', Lake Placid, NY 12946, USA. Antibody Class: IgG1k. Immunogen: HPC purifed human sperm phospholipase A(2)- 14 kDa enzyme) using the standard DAKO peroxidase-labelled streptavidin-biotin method by TechMate 500 stainer. Group II PLA(2)expression was evaluated semi-quantitatively according to the extensivity and intensivity of the positive cells. For statistical evaluation the Kruskal-Wallis one way analysis of variance on ranks and the Mann-Whitney rank sum tests were used. RESULTS: The highest expression of group II PLA(2)was found in the peritumoural mucosa (median 4.00), much lower in the mucosa distal from the tumour (median 0.70) and almost no activity in the tumour itself (median 0.00), all differences were statistically significant (all pairwise multiple comparison procedures - Dunn's Method P<0.05). The expression of group II PLA(2)was higher in the left colon and rectum than in the right colon (Mann-Whitney rank sum test P<0.05). CONCLUSIONS: Our results suggest that there is variation of the group II PLA(2)expression throughout the mucosa and tumours of the colorectum, which might reflect the progression of neoplastic process.