The introduction of imatinib to clinical practice revolutionized therapy of advanced gastrointestinal stromal tumors (GIST), but its long-term results have been only just collected. We have attempted to identify factors related to the long-term survival. We have analyzed the data of 430 inoperable/metastatic/recurrent GIST patients treated with imatinib in reference centers, assessed the factors influencing the long-term overall survival (OS), and compared the outcomes in three periods of initiation of imatinib therapy during one decade (2001–2003, 2004–2006, 2007–2010). During analyzed time periods, we have found decrease in median largest tumor size at the start of imatinib therapy: 90.5 mm (2001–2003) versus 74 mm (2004–2006) versus 58 mm (2007–2010) (p = 0.002). Median progression-free survival (PFS) on 1st line imatinib was 37.5 months, without differences in PFS between three groups. Median OS was 5.8 years, 8-year OS rate was 43 %, and no difference in OS was demonstrated for patients treated in analyzed time periods. Independent good prognostic factors for longer OS were as follows: surgery of residual disease, initial WHO performance status 0/1, normal baseline albumin level, and the presence of exon 11 KIT mutations. Current median OS in advanced GIST reaches 6 years. The long-term survivors were characterized by smaller maximal tumors at imatinib start, better blood tests results, better performance status, and the surgical removal of residual disease. The latter might reduce the impact of tumor size and equalize the long-term results of therapy during last decade from introduction of imatinib. After introduction of subsequent lines of therapy (as sunitinib), the effect of primary mutational status on the long-term OS is also less visible.

Aim of the studywas to analyze the outcome of treatment and factors predicting results of sorafenib therapy in inoperable/metastatic CD117-positive GIST patients after failure on imatinib and sunitinib.Material and methodsWe identified 60 consecutive patients (40 men, 20 women) with advanced inoperable/metastatic GIST after failure on at least imatinib and sunitinib treated in one sarcoma center with sorafenib at initial dose 2 × 400 mg daily in 2007–2015 (in 56 cases it was 3rd line therapy). Median follow-up time was 39 months.ResultsOne year progression-free survival (PFS; calculated from the date of the start of sorafenib to disease progression) rate was 23% and median PFS = 7.7 months. The median overall survival (OS) was 13.5 months calculated from sorafenib start (1-year OS rate = 57%) and 7 years from imatinib start. Three patients (5%) had objective partial responses to therapy, 31 patients (52%) had stabilization of disease > 4 months. Primary tumor mutational status was known in 43 cases (73%), but we have not identified the differences in PFS between tumors carrying different KIT/PDGFRA mutations. The most common adverse events were: diarrhoea, hand and foot syndrome, fatigue, loss of weight and skin reactions; grade 3–5 toxicity occurred in 35% of patients. 23 patients required sorafenib dose reductions due to AEs.ConclusionsWe confirmed that many advanced GIST patients benefit from sorafenib therapy after imatinib/sunitinib failure with OS > 1 year.

Introduction. A rare variant of chromosomal region 15q25.1, marked by rs16969968 (substitution 1354G>A or D398N in CHRNA5 gene), was found to be associated with increased lung cancer risk and nicotine dependence appearance. We attempted to confirm the relationship between polymorphism of gene for nicotine acetylocholine receptor A subunit 5 (CHRNA5) and stage of nicotine dependence measured by the result of Fagerström test and cotinine level in serum in lung cancer, COPD and healthy smokers. Methods. Polymorphism of CHRNA5 gene was analised using PCR-RFLP method in the group of 97 lung cancer patients, 99 COPD patients and 98 healthy volunteers. The Fagerström Test for Nicotine Dependence was used as a standard instrument for assessing the intensity of this physical addiction. Cotinine serum level was measured using ELISA method. Results. In all analyzed subjects, the frequency of AA, AG and GG genotypes were 11%, 47% and 42%, respectively. The polymorphism of CHRNA5 gene does not have a significant influence on the elevated risk of lung cancer and COPD. The presence of GG genotype decreased the risk of strength of nicotine addiction (HR=0.238, 95%CI:[0.066–0.857], p<0.05). We observed that allele A was presented more frequently in the subjects with high level of nicotine dependence and in the subjects with early (<25 years) onset of addiction (p<0.05). Moreover, cotinine serum level significantly correlated with results of Fagerström test (p<0.001). The carriers of allele A expressed significantly higher level of serum cotinine when compared with the carriers of GG genotype (p=0.05). Conclusion. In the presented abstract we report for the first time the relationship between the polymorphism of CHRNA5 gene and the strength of nicotine addiction. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-449. doi:10.1158/1538-7445.AM2011-LB-449

No abstract