The analysis of the long-term outcomes of sorafenib therapy in routine practice in imatinib and sunitinib resistant gastrointestinal stromal tumors (GIST).

AIM OF THE STUDY: was 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 METHODS: We 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. RESULTS: One 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. CONCLUSIONS: We confirmed that many advanced GIST patients benefit from sorafenib therapy after imatinib/sunitinib failure with OS > 1 year.

What are the current outcomes of advanced gastrointestinal stromal tumors: who are the long-term survivors treated initially with imatinib?

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.

[Influence of tumor diameter on treatment results in cervical cancer patients]. / Wplyw wielkosci guza nowotworowego na wyniki leczenia chorych na raka szyjki macicy.

UNLABELLED: The impact of the tumor size on treatment outcomes in cervical cancer patients remains a subject of controversy OBJECTIVES: The assessment of prognostic value of pretreatment tumor size in cervical cancer patients. MATERIALS AND METHODS: Patients of Maria Sklodowska - Curie Memorial Cancer Centre in Warsaw, treated between January 1996 and December 2000, were included into the retrospective study. 242 patients were diagnosed with a histologically confirmed squamous cell carcinoma and 42 with adenocarcinoma, FIGO staged IB-IVA, having undergone the clinical assessment and USG examination of the tumor treated with curative intent with surgery and/ or radiotherapy. The widest tumor diameter was adopted as the tumor size. In most cases of adenocarcinoma, the tumors were described as endocervical and the tumor measurement was connected with the risk of mistake, therefore, the analysis of the squamous cell cancer patients only was performed. A multivariate analysis of 242 patients with regard to overall survival (OS) and disease-free survival (DFS), depending on the selected clinico-pathological factors, was performed. The mean potential follow-up time for surviving patients was 50 months (range 8.7-62). The 5-year overall survival (OS) rate was 62%. RESULTS: As the result of the multivariate analysis, the impact of FIGO stage (p=0.002), hemoglobin pretreatment concentration (p=0.031) and tumor size before treatment (p = 0.044) on OS, and FIGO stage (p=0.001), hemoglobin level before treatment (p=0.019) on DFS, was demonstrated. CONCLUSIONS: Tumor diameter before treatment in squamous cell cervical cancer patients provides important prognostic information, regardless of other prognostic factors.