Circulating tumor cells (CTCs) provide a non-invasive accessible source of tumor material from patients with cancer. The cellular heterogeneity within CTC populations is of great clinical importance regarding the increasing number of adjuvant treatment options for patients with metastatic carcinomas, in order to eliminate residual disease. Moreover, the molecular profiling of these rare cells might lead to insight on disease progression and therapeutic strategies than simple CTCs counting. In the present study we investigated the feasibility to detect KRAS, BRAF, CD133 and Plastin3 (PLS3) mutations in an enriched CTCs cell suspension from patients with colorectal cancer, with the hypothesis that these genes` mutations are of great importance regarding the generation of CTCs subpopulations. Subsequently, we compared CTCs mutational status with that of the corresponding primary tumor, in order to access the possibility of tumor cells characterization without biopsy. CTCs were detected and isolated from blood drawn from 52 colorectal cancer (CRC) patients using a quantum-dot-labelled magnetic immunoassay method. Mutations were detected by PCR-RFLP or allele-specific PCR and confirmed by direct sequencing. In 52 patients, discordance between primary tumor and CTCs was 5.77% for KRAS, 3.85% for BRAF, 11.54% for CD133 rs3130, 7.69% for CD133 rs2286455 and 11.54% for PLS3 rs6643869 mutations. Our results support that DNA mutational analysis of CTCs may enable non-invasive, specific biomarker diagnostics and expand the scope of personalized medicine for cancer patients.
The CC genotype of rs3130 polymorphism in the CD133 gene can predict poorer overall survival in patients with metastatic CRC on bevacizumab which cannot be attributed to increased treatment toxicity.
The clinical significance of the findings requires replication in larger populations. Furthermore, as 5.FU and irinotecan metabolism is complex, numerous genes in addition to DPD and UGT1A1 should be investigated.
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e23150 Background: Cancer is associated with thrombosis due to different pathophysiological processes. CAT is the 2nd cause of death in oncology patients and can occur anytime during the natural history of cancer. CAT is not rare complication, can delay anti-cancer therapy and increase health systems costs. Methods: A prospective observational study (Greek Management of Thrombosis-GMaT) conducted by HeSMO in Greek Oncology units for two years aiming to record clinical practice of CAT management. Patients with active cancer who received CAT treatment or thromboprophylaxis were enrolled after signing informed consent. Results: 546 patients were enrolled from 18 oncology units. Primary cancers were: lung 23.9%, pancreas 13.3%, breast 7.6%, colorectal 8.9%, stomach 8.3%, ovarian 7.6% and other 30.5%. 120 patients received LMWH for Venus Thombo-Embolism (VTE) treatment (Group A) and 426 for thromboprophylaxis (Group B). Group A: 89/120 (74.17%) patients continued in 2nd year and 58.6% received CAT treatment (6.9±4.4 months). Only 2 had VTE recurrence in 2nd year (versus 3 in 1st year). 4/120 (3.33%) had bleeding events (grade 1) in 1st year while no bleeding events occurred in 2nd year. Group B: 345/426 (80.98%) patients continued in 2nd year. 126 (30%) had Khorana score ≥3 and 300 (70%) had Khorana score ≤2. In 2nd year, 123 (35.65%) received thromboprophylaxis (7.3±3.7 months) while 79.4% of them were initially treated with High Thrombotic Treatment Agents (HTTA: e.g. platinum, 5-FU) and 83.1% had metastatic disease. In 2nd year, 52.5% received LMWHs at prophylactic dose and 47.5% at therapeutic dose. Overall, 12 (2.82%) had thrombotic events whereas 4 were recorded in 2nd year. Notably, patients treated with therapeutic doses had lower probability to have a thrombotic event (OR: 5.8, 95% CI: 1.7 to 20.5, p < .05). Six (1.41%) bleeding events (grade 1) occurred in 1st year and one (0.81%) in 2nd year. Conclusions: LMWHs can be used for long term CAT management. Therapeutic LMWHs doses as thromboprophylaxis are safe and effective. Khorana score is a useful model for CAT risk assessment but some other factors such as disease stage and HTTA might be taken into account. CAT can occur anytime during the natural history of cancer. Oncologists should be aware about CAT and its negative influences in patients’ prognosis and quality of life.
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