Risk factors for cancer-associated thrombosis are commonly divided into three categories: patient-, cancer-, and treatment-related factors. Currently, different types of drugs are used in cancer treatment. Chemotherapy has been identified as an independent risk factor for venous thromboembolism (VTE). However, it should be noted, that the risk of VTE is not consistent among all cytotoxic agents. In addition, different supportive care drugs, such as erythropoiesis stimulating agents or granulocyte colony stimulating factors, and hormonotherapy have been associated to an increased risk of VTE. Immunotherapy and molecular-targeted therapies have significantly changed the treatment of cancer over the past decade. The main subtypes include tyrosine-kinase inhibitors, monoclonal antibodies, small molecules, and immunomodulatory agents. The relationship between VTE and targeted therapies remains largely unknown.
59 Background: Over the last decades the incidence of EOCRC (age 50 or less) has dramatically increased, and so has the scientific interest in this field, given that clinical and molecular characteristics in these patients are not well understood, and may be critical to identify prognostic factors. Methods: We conducted a retrospective analysis of 554 patients with metastatic colorectal cancer (mCRC), analyzing the PFS and OS of 68 (12.25%) patients with EOCRC, as well as their clinical and molecular characteristics. We used a log-rank test to compare PFS and OS, and the estimate of hazard ratio (HR) between the studied groups was calculated by means of Cox proportional hazard model. We also used the exact test of Fisher to identify significant association between categoric variants, while Mann-Whitney test was applied to identify significant differences between numeric values. Results: We performed a survival analysis: those patients with EOCRC had significantly higher median PFS in first line of treatment (16.2 vs. 11.3 months, p = 0.042) and significantly higher median OS (121.5 vs. 58.1 months, p = 0.011). Several characteristics were significantly more frequent in patients with EOCRC (n=68): BMI < 18.5 (n = 16, OR = 1.9, p = 0.046), primary tumor site at transverse colon (n = 9, OR = 2.61, p = 0.03) and ECOG 0 (n = 32, OR = 2.21, p = 0.003). Having peritoneal metastases almost reached statistical signification (n = 17, OR = 1.82, p = 0.055). Some other characteristics were less frequent: BMI 25-30 (n = 13, OR = 0.51, p = 0.046), primary tumor site at sigmoid colon (n = 14, OR = 0.49, p = 0.038) and former-smoker status (n = 7, OR = 0.44, p = 0.048). Moreover, mean values of LDH at diagnosis were significantly higher in EOCRC patients (359 U/L vs. 280 U/L, p = 0.015). EOCRC patients received a significantly higher number of lines of chemotherapy (2.94 vs. 2.38, p = 0.027) and underwent more surgeries (2,42 vs. 1.24, p < 0,001) than patients with > 50 years. Significant differences in tumor mutational status (BRAF, KRAS, NRAS, MSI, PI3K and HER2), sex, primary tumor resection or number of metastatic sites between groups were not found. Conclusions: This retrospective analysis showed that EOCRC patients had significant higher rates of PFS in first-line treatment and OS. Moreover, EOCRC patients had more frequently BMI < 18.5, primary tumor located at transverse colon and ECOG 0.
4041 Background: Approximately 25% of patients with colorectal cancer (CRC) debut with metastatic disease. In addition, 25-35% of patients with localized disease at diagnosis develop metastatic lesions during the evolution of their disease. Consequently, approximately 50-60% of patients with CRC will present metastatic lesions at some point in their lives. Metastasis resection has improved the prognosis of these patients, achieving overall survival (OS) that exceed 40 months. However, there are doubts about the benefit of this approach in patients with mutations in oncogene BRAF or tumors located on the right-side, due their poor prognosis. The aim of the study is to analyze the impact of metastases resection on OS of these populations. Methods: We conducted a retrospective analysis of patients with mCRC attended in the Medical Oncology Department of the Hospital General Universitario Gregorio Marañón (Spain) between January 2010 and 2018. Results: 487 patients were identified and included in the analysis. Median age was 71 years (62-81). Most patients were males (62.4%). 55.2% had metastatic lesions at diagnosis. Most patients had ECOG 0-1 at diagnosis of metastatic disease (91.0%). 8.9% of patients had BRAF mutations (n = 21) and 31.8% of patients had primary tumors located on the right-side (n = 152). 474 patients received first-line chemotherapy (97.3%). OS of the entire cohort was 29.67 months; 30.69 months in BRAF mutated patients vs 35.89 in wild-type patients (p = 0.161); 25.29 months in right-side tumors vs 31.02 in left-side tumors (p = 0.044). 306 patients (62.8%) underwent metastases resection. Most common location was liver (51.4%). 147 patients (30.2%) underwent a second metastases resection. Mean number of metastases surgeries was 1.35 (+/-1.40). OS since metastases resection was 24.83 months in BRAF mutated patients vs 41.55 months in wild-type patients (p = 0.020). According to location, it was 35.49 months in right-side tumors vs 43.78 months in left-side tumors (p = 0.106). In BRAF mutated patients, OS was 38.19 months in patients underwent metastases resection vs 18.52 months in non-surgical patients (p = 0.043); 41.51 months vs 16.18 months respectively in patients with tumors located on the right-side (p < 0.001). Conclusions: Metastases resection has a positive impact on overall survival of patients with mutations in oncogene BRAF or right-side tumors, even though their prognosis is still poor compared to patients without these alterations.
Uncommon EGFR mutations were observed in 38 patients, comprising approximately 10% of all EGFRmut + NSCLC patients (348) diagnosed and treated in Alberta, Canada (2010-2017. Of the total 38 patients, 63% were female, 60% had a smoking history, and 75% were Canada-born. Dual/-triple mutation positivity was found in 40% of patients. 4/38 patients expired prior to receiving any form of palliative treatment. Upon classifying patients as per TKI treatment, it was found that most received gefitinib (67%) as first line systemic palliative treatment (Table 2). Median OS of the entire cohort was 15.1 months; meanwhile those with complex double/-triple mutations experienced longer mOS of 24.9months vs 11.8months for single uncommon carriers. Conclusion: This Canadian study supports that uncommon EGFR mutation carriers are infrequent in clinical lung cancer practice. Of note, they represent a unique sub-population amongst EGFRmut + NSCLC patients, and experience differential sensitivity and varied responses to treatment. We observed favorable responses to EGFR-TKIs in patients with double/-triple uncommon mutations, supporting that these patients may benefit from EGFR-TKIs.
e15552 Background: BRAF mutated mCRC patients have worse prognosis compared with BRAF wildtype mCRC. Within this group, those with resectable disease have a better prognosis compared to those with unresectable disease. However, it is not well known whether there are clinical differences that may help clinicians to identify this subgroup of patients. Methods: We conducted a retrospective analysis of 24 patients with BRAF mutated mCRC, describing their clinical characteristics and the differences between those who have undergone metastatic surgery (n = 18) versus those who have not (n = 6). We applied the exact test of Fisher to identify significant association between categoric variables, while we used Mann-Whitney test to identify significant differences between quantitative variables. PFS and OS were compared using a long-rank test, and the estimate of hazard ratio (HRs) between studied groups was calculated by means of Cox proportional hazards model. Results: Twenty-four patients with BRAF mutated mCRC have been identified. 58% (n = 14) of them were < 65 years old; 54% (n = 13) had BMI > 25, and all of them had a good PS at diagnosis (0 or 1). The most frequent tumor location was the right colon (58%; n = 14) and in 79% (n = 19) of the cases the primary tumor was resected. Most of the patients presented peritoneal (41%, n = 10) or liver (41%, n = 10) disease, and 70% of them (n = 17) had synchronous disease. Within the 18 patients who underwent surgery, the most frequent surgery was liver metastasectomy (50%, n = 9) followed by peritoneal metastasectomy (28%, n = 5). Regarding first-line chemotherapy treatment, only 12% (n = 3) presented disease progression in the first reassessment. No statistically significant differences were found between surgical and non-surgical patients regarding the following variables: age, BMI, ECOG, primary tumor side, location of the metastases, synchronous presentation of the metastatic disease, analytical parameters (CEA, Ca 19.9 and LDH), response to chemotherapy treatment and first line progression-free survival. However, we found significant differences in overall survival with an HR for mortality of 0.22 (95% CI 0.049-0.99; p = 0.031) in patients undergoing metastases surgery, with a median of 38 months in patients who underwent surgery vs 20 months in those who did not. Conclusions: BRAF mutated mCRC who receive surgery for metastases have better prognosis with higher overall survival, compared to those who have not undergone surgery. Still, no other statistically significant differences were found in the rest of the clinical characteristics analyzed to identify a subgroup with better prognosis.
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