Neoadjuvant concomitant chemoradiotherapy has become a standard treatment of locally advanced rectal adenocarcinomas (LARA). It leads to shrinkage of the tumor mass and subsequently to an increase in complete resections (R0 resections), increasing a feasibility of sphincter-sparing intervention avoiding colostomy. It is based on concurrent application of fluoropyrimidines (5-fluorouracil, capecitabine) and radiotherapy (45 - 50,4 Gy). It shows less acute toxicity and improves local control rate in comparison to adjuvant treatment. Unfortunately, neoadjuvant chemoradiotherapy is not beneficial for all patients. The treatment response ranges from a complete pathological remission (pCR, ypT0ypN0) to a resistance. It is reported that cca 15 percent of patients with advanced rectal cancer show pCR which is indicative of improved long-term prognosis. DESIGN: The following is a review of the significance of neoadjuvant concomitant chemoradiotherapy in the treatment algorithm of patients with LARA and summary of potentional clinical-pathological and molecular markers of response prediction to neoadjuvant therapy. The most important clinical studies concern serum tumor markers levels, clinical lymph node classification. The components of the carcinogenic pathways are explored, including oncogenes, tumor supressor genes, microsatellite instability (MSI) and potentional markers involved in apoptosis, angiogionesis, proliferation as well as metastasis and invasion, are reviewed. Finally, the role of specific enzymes associated with the metabolism of fluoropyrimidines are examined. CONCLUSIONS: No one marker has been consistently identified as clinically applicable. Studies designed to determine the potentional markers are hampered by various techniques as well as tumor heterogenity and recent scientific approach--studying individual molecular markers. Gene expression profiling analysis of multiple genes from the same tumor is becoming reality. We suppose that this assessment will lead in future in finding combination of markers for predicting prognosis and response to therapy in rectal cancer., Garajová Ingrid, Svoboda M., Slabý O., Kocáková L., Fabian P., Kocák I., Vyzula R., and Lit.: 71
Úvod: Reverzný, liver-first prístup je alternatívou pre pacientov s komplikovanými synchrónnymi pečeňovými metastázami, kde by progresia v pečeni viedla k inoperabilite, alebo pre pacientov s lokálne pokročilým nálezom v malej panve, kde by komplikácia resekcie primárneho tumoru mohla ohroziť včasnú resekciu pečeňových metastáz. Metódy: Retrospektívna unicentrická analýza 32 pacientov liečených reverzným prístupom v období rokov 2011−2015. Reverzný prístup bol v tomto období indikovaný na základe konsenzu členov multioborovej onkologickej komisie ako preferovaný u všetkých pacientov s iniciálne, alebo potenciálne resekabilným synchrónnym izolovaným metastatickým postihom pečene pri adenokarcinóme kolorekta. Výsledky: 26 pacientov (81,3 %) úspešne absolvovalo kompletnú resekciu nádorovej masy (resekciu pečeňových metastáz a resekciu primárneho tumoru), ale iba 16 pacientov (50 %) absolvovalo kompletný onkochirurgický liečbený plán (hepatektómia, resekcia primárneho tumoru a plánovaná dávka a dĺžka perioperačnej, alebo adjuvantnej onkologickej liečby). Medián prežívania bol 50,5 mesiacov, trojročné prežívanie v súbore bolo 83,7 %. U 20 pacientov (62,5 %) došlo počas sledovania k progresii ochorenia s mediánom do progresie 21,6 mesiaca. Najčastejším miestom progresie bola pečeň, nasledovaná pľúcami (65 resp. 20 % všetkých rekurencií nádorového ochorenia). Záver: Aj keď reverzný, liver-first prístup umožňuje kompletné odstránenie masy tumoru u väčšiny pacientov, iba polovica z nich absolvuje kompletný onkochirurgický liečebný plán. Najproblematickejším aspektom reverzného postupu je načasovanie a dĺžka perioperačnej (bio)chemoterapie. Dôkladné zváženie rizika progresie metastatického procesu počas liečby ako aj rizika kompletnej rádiologickej odpovede by malo viesť k uváženej indikácii perioperačnej (bio)chemoterapie najmä u pacientov s iniciálne resekabilnými pečeňovými metastázami., Introduction: Reverse, liver-first strategy is an alternative for patients with complicated liver metastases where disease progression would prove inoperable, or for patients with locally advanced pelvic disease where postoperative complications after primary tumour resection may lead to delayed treatment of metastatic disease. Methods: Retrospective unicenter analysis of 32 patients approached liver-first approach between 2011 and 2015. During this period reverse strategy was considered a preferred approach for all initially or potentially resectable synchronous colorectal liver metastases based on multidisciplinary team consensus. Results: 26 patients (81.3%) completed their surgical plan (hepatectomy and primary tumour resection) but only 16 (50%) completed their oncosurgical plan (hepatectomy, primary tumour resection and full dose and length of perioperative or adjuvant systemic (bio)chemotherapy). Median overall survival was 50.5 months with the survival rate of 83.7% at 3 years. 20 patients (62.5%) progressed during the follow-up with median time to progression of 21.6 months. The liver was the most common site of recurrent disease followed by the lungs (65% and 20% of all recurrences, respectively). Conclusion: While reverse strategy may allow complete tumour removal in the majority of patients, only half of them complete their oncosurgical plan even with the liver-first approach. The most problematic aspect of the liver-first strategy is the timing and length of perioperative (bio)chemotherapy. When deciding on preoperative chemotherapy in up-front resectable lesions one should take into account the risk of disease progression while on chemotherapy as well as the risks of complete radiologic response., and M. Straka, M. Migrová, R. Soumarová, L. Burda, I. Selingerová